Study of the radiofrequency-induced heating inside the human head with dental implants at 7 T.
Conductive dental implants are commonly used in restorative therapy to replace missing teeth in patients. Ensuring the radiofrequency (RF) safety of these patients is crucial when performing 7 T magnetic resonance scans of their heads. This study aimed to investigate RF-induced heating inside the human head with dental implants at 7 T. Dental implants and their attachments were fabricated and integrated into an anatomical head model, creating different measurement configurations (MCs). Numerical simulations were conducted using a 7 T transmit coil loaded with the anatomical head model, both with and without dental implants. The maximum temperatures inside the head for various MCs were computed using the maximum permissible input powers (MPIPs) obtained without dental implants and compared with published limits. Additionally, the MPIPs with dental implants were calculated for scenarios where the temperature limits were exceeded. The maximum temperatures observed inside the head ranged from 38.4°C to 39.6°C. The MPIPs in the presence of dental implants were 81.9%-97.3% of the MPIPs in the absence of dental implants for scenarios that exceeded the regulatory limit. RF-induced heating effect of the dental implants was not significant. The safe scanning condition in terms of RF exposure was achievable for patients with dental implants. For patients with conductive dental implants of unknown configuration, it is recommended to reduce the input power by 18.1% of MPIP without dental implants to ensure RF safety.


Fine mapping and candidate gene analysis of qTAC8, a major quantitative trait locus controlling tiller angle in rice (Oryza sativa L.).
Rice tiller angle is an important agronomic trait that contributes to crop production and plays a vital role in high yield breeding. In this study, a recombinant inbred line (RIL) population derived from the cross of a glabrous tropical japonica rice D50 and an indica rice HB277, was used to investigate quantitative trait loci (QTLs) controlling rice tiller angle. Two major QTLs, qTAC8 and qTAC9, were detected. While qTAC9 mapped with a previously identified gene (TAC1), using a BC2F2 population qTAC8 was mapped to a 16.5 cM region between markers RM7049 and RM23175. Position of qTAC8 was narrowed to a 92 kb DNA region by two genetic segregating populations. Finally, one opening reading frame (ORF) was regarded as a candidate gene according to genomic sequencing and qRT-PCR analysis. In addition, a set of four near isogenic lines (NILs) were created to investigate the genetic relationship between those two QTLs, and one line carrying qTAC8 and qTAC9 presented additive effect of tiller angle, suggesting that these QTLs are involved in different genetic pathways. Our results provide a foundation for the cloning of qTAC8 and genetic improvement of the rice plant architecture.


Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.
In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramat's bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures. All of the analogues have been identified on the basis of (1)H NMR, ESI-MS and elemental analysis data. The activities of these analogues were evaluated against three organisms, and biological assays indicated that compounds 5f, 5h and 5u possessed better insecticidal activities against bean aphids (Aphis fabae) than the lead compound spirotetramat. The LC50 of 5f, 5h and 5u against bean aphids reached 0.42, 0.28 and 2.53 mg L(-1) respectively. Moreover, some compounds possessed comparable activities against carmine spider mite (Tetranychus cinnabarinus) and oriental armyworm (Mythimna sepatara) with spirotetramat. The structure-activity relationships (SARs) indicated that the flexible bridge at position C-4 of spirotetramat was important for its bioactivities, and the size of the group at position C-8 would have great influence on the activities. Furthermore, the log P values lower than 6.0 may be favourable for insecticidal activities. The present work demonstrates that some spirotetramat analogues can be used as potential lead compounds for developing novel insecticides, and preliminary SAR analysis would provide information for the utilisation of spirotetramat analogues as potential lipid biosynthesis inhibitors.


Material and mechanical factors: new strategy in cellular neurogenesis.
Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharmacological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material (chemical patterning, micro/nano-topography, carbon nanotube, graphene) and mechanical (static cue from substrate stiffness, dynamic cue from stretch and flow shear) stimulations of cellular neurogenesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.


Antenatal corrective cardiac surgery: An emerging area for technological innovation.
The possibility of intervening in utero on certain cardiac malformations with the intent to prevent secondary major alterations in structure and function is becoming a reality. Central to progress in this area is the development of instrumentation specifically designed for minimally invasive cardiac surgery in the fetus. The present review introduces a novel set of devices for interventional cardiology, based on current knowledge and prior experience, and highlights their prospective application. In meeting this objective, particular importance is assigned to the synergic contribution of diverse disciplines, both medical and nonmedical.


CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus.
SINE-VNTR-Alu (SVA) retrotransposons are hominid-specific elements which have been shown to play important roles in processes such as chromatin structure remodelling and regulation of gene expression demonstrating that these repetitive elements exert regulatory functions. We have previously shown that the presence or absence of a specific SVA element, termed SVA_67, was associated with differential expression of several genes at the MAPT locus, a locus associated with Parkinson's Disease (PD) and frontotemporal dementia. However, we were not able to demonstrate that causation of differential gene expression was directed by the SVA due to lack of functional validation. We performed CRISPR to delete SVA_67 in the HEK293 cell line. Quantification of target gene expression was performed using qPCR to assess the effects on expression in response to the deletion of SVA_67. Differences between CRISPR edit and control cell lines were analysed using two-tailed t-test with a minimum 95% confidence interval to determine statistical significance. In this study, we provide data highlighting the SVA-specific effect on differential gene expression. We demonstrate that the hemizygous deletion of the endogenous SVA_67 in CRISPR edited cell lines was associated with differential expression of several genes at the MAPT locus associated with neurodegenerative diseases including KANSL1, MAPT and LRRC37A. This data is consistent with our previous bioinformatic work of differential gene expression analysis using transcriptomic data from the Parkinson's Progression Markers Initiative (PPMI) cohort. As SVAs have regulatory influences on gene expression, and insertion polymorphisms contribute to interpersonal differences in expression patterns, these results highlight the potential contribution of these elements to complex diseases with potentially many genetic components, such as PD.


Physical inactivity in nine European and Central Asian countries: an analysis of national population-based survey results.
Physical inactivity is a major risk factor for non-communicable diseases. However, recent and systematically obtained national-level data to guide policy responses are often lacking, especially in countries in Eastern Europe and Central Asia. This article describes physical inactivity patterns among adults in Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkey and Uzbekistan. Data were collected using the Global Physical Activity Questionnaire drawing nationally representative samples of adults in each country. The national prevalence of physical inactivity was calculated as well as the proportional contribution to total physical activity (PA) during work, transport and leisure-time. An adjusted logistic regression model was applied to analyze the association of age, gender, education, household status and income with physical inactivity. National prevalence of physical inactivity ranged from 10.1% to 43.6%. The highest proportion of PA was registered during work or in the household in most countries, whereas the lowest was during leisure-time in all countries. Physical inactivity was more likely with older age in eight countries, with female gender in three countries, and with living alone in three countries. There was no clear pattern of association with education and income. Prevalence of physical inactivity is heterogeneous across the region. PA during leisure-time contributes minimally to total PA in all countries. Policies and programs that increase opportunities for active travel and leisure-time PA, especially for older adults, women and people living alone will be an essential part of strategies to increase overall population PA.


Extranodal lymphoma with an unusual constellation of features.
Hypercalcemia, lytic bone lesions, and hematogenous dissemination formed an unusual constellation of presenting features in a patient with extranodal non-Hodgkin's lymphoma. The patient's clinical course was short, with death resulting nine months after diagnosis, and this combination of features may indicate a poor prognosis.


Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles to Treat PCOS.
Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in women. Previously, we suggested that human mesenchymal stem cells (MSCs) can reverse the PCOS condition by secreting factors. Here, we evaluated the therapeutic capability of MSC-derived extracellular vesicles (EVs), also known as exosomes, in both in vitro and in vivo PCOS models. Exosomes were used to treat androgen-producing H293R cells and injected in a mouse model through intraovarian and intravenous injection into a letrozole (LTZ)-induced PCOS mouse model. We assessed the effects of the exosomes on androgen-producing cells or the PCOS mouse model by analyzing steroidogenic gene expression (quantitative real-time polymerase chain reaction (qRT-PCR)), body weight change, serum hormone levels, and fertility by pup delivery. Our data show the therapeutic effect of MSC-derived EVs for reversing PCOS conditions, including fertility issues. Interestingly, intravenous injection was more effective for serum glucose regulation, and an intraovarian injection was more effective for ovary restoration. Our study suggests that MSC-derived exosomes can be promising biopharmaceutics for treating PCOS conditions as a novel therapeutic option. Despite the fact that we need more validation in human patients, we may evaluate this novel treatment option for PCOS with the following clinical trials.


Combination of acupuncture and spinal manipulative therapy: management of a 32-year-old patient with chronic tension-type headache and migraine.
The purpose of this case study is to describe the treatment using acupuncture and spinal manipulation for a patient with a chronic tension-type headache and episodic migraines. A 32-year-old woman presented with headaches of 5 months' duration. She had a history of episodic migraine that began in her teens and had been controlled with medication. She had stopped taking the prescription medications because of gastrointestinal symptoms. A neurologist diagnosed her with mixed headaches, some migrainous and some tension type. Her headaches were chronic, were daily, and fit the International Classification of Headache Disorders criteria of a chronic tension-type headache superimposed with migraine. After 5 treatments over a 2-week period (the first using acupuncture only, the next 3 using acupuncture and chiropractic spinal manipulative therapy), her headaches resolved. The patient had no recurrences of headaches in her 1-year follow-up. The combination of acupuncture with chiropractic spinal manipulative therapy was a reasonable alternative in treating this patient's chronic tension-type headaches superimposed with migraine.


Convenient synthesis and characterization of silane-capped polysiloles for the fabrication of luminescent OLED.
Catalytic dehydropolymerization and subsequent silane-capping with R2SiHCI (R = Ph, Me) of 1,1-dihydrotetraphenylsilole (1) using various inorganic hydrides produces electroluminescent silane-capped polysiloles (2) in high yield. The polymerization yield and molecular weight increase in the order LiB[CH(CH3)C2H5]3H < NaB[CH(CH3)C2H5]3H < KB[CH(CH3)C2H5]3H. The molecular weights increase in the order Na[H2Al(OCH2CH2OCH3)2] < KB[CH(CH3)C2H5]3H < LiB(C2H5)3H. The silane-capped polysiloles 2 emit at 521 nm and are electroluminescent at 522 nm. The fluorescence quantum yield of 2 in toluene is (1.67 +/- 0.31) x 10(-2). The emission color is green and the maximum brightness of the device is 2900 cd/m2 with a luminous efficiency of 0.69 lm/W. The substituent type of silyl end group showed no appreciable effect on the luminescent properties of polysilole backbone. Thus, the silane-capped polysiloles are found to be a good material for OLED fabrication. A possible mechanism for the formation of 2 was suggested.


Network-based approaches for the investigation of microbial community structure and function using metagenomics-based data.
Network-based approaches offer a powerful framework to evaluate microbial community organization and function as it relates to a variety of environmental processes. Emerging studies are exploring network theory as a method for data integration that is likely to be critical for the integration of 'omics' data using systems biology approaches. Intricacies of network theory and methodological and computational complexities in network construction, however, impede the use of these tools for translational science. We provide a perspective on the methods of network construction, interpretation and emerging uses for these techniques in understanding host-microbiota interactions.


Observation of quantum recoherence of photons by spatial propagation.
Entanglement is at the heart of many unusual and counterintuitive features of quantum mechanics. Once two quantum subsystems have become entangled, it is no longer possible to ascribe an independent state to either; instead, the subsystems are completely described only as part of a greater, composite system. As a consequence of this, each entangled subsystem experiences a loss of coherence following entanglement. We refer to this decrease in coherence as decoherence. Decoherence leads inevitably to the leaking of information from each subsystem to the composite entangled system. Here, we demonstrate a process of decoherence reversal, whereby we recover information lost from the entanglement of the optical orbital angular momentum and radial profile degrees of freedom possessed by a photon pair. These results carry great potential significance, since quantum memories and quantum communication schemes depend on an experimenter's ability to retain the coherent properties of a particular quantum system.


Clinical trial with a percutaneously inserted intra-aortic balloon pump: a wider spectrum of patient application.
The intra-aortic balloon pump has been proven to be an effective form of therapy in a variety of situations involving actual or potential ventricular power failure. An experience with 12 newly-designed percutaneous PERCOR-TM intra-aortic balloon pumps is discussed. Emphasis is made on the ease of insertion and removal, and on the fact that a trained surgical team in an operating room setting is not necessary. Effectiveness of the balloon in comparison to the traditional intra-aortic balloon pump is also discussed.


Two objects or one? Similarity rather than complexity determines objecthood when resolving dynamic input.
The human brain is continuously confronted with dynamic visual input, and from this it must infer whether input belongs to a single versus multiple object identities across time. Object substitution masking (OSM), in which perception of a target stimulus is impaired by a temporally trailing 4-dot mask, reflects a failure to segment the target and mask as discrete objects. According to Bouvier and Treisman (2010), OSM only occurs for targets that require binding multiple separate features (e.g., color and orientation) to be identified. In contrast, a target that represents a unique feature is thought to be impervious to masking. Here, however, we show that a single orientation target (a Gabor) is susceptible to masking with an orientation-discrimination task, but only when the mask is similar in orientation to the target. That is, target-mask similarity, rather than target complexity determines masking. A reexamination of Bouvier and Treisman's (2010) results show that they can be explained within this target-mask similarity perspective. This means that the similarity of 2 objects determines whether they will be integrated or segmented across time, rather than the complexity of 1 of the objects in isolation.


Research of Hubs Location Method for Weighted Brain Network Based on NoS-FA.
As a complex network of many interlinked brain regions, there are some central hub regions which play key roles in the structural human brain network based on T1 and diffusion tensor imaging (DTI) technology. Since most studies about hubs location method in the whole human brain network are mainly concerned with the local properties of each single node but not the global properties of all the directly connected nodes, a novel hubs location method based on global importance contribution evaluation index is proposed in this study. The number of streamlines (NoS) is fused with normalized fractional anisotropy (FA) for more comprehensive brain bioinformation. The brain region importance contribution matrix and information transfer efficiency value are constructed, respectively, and then by combining these two factors together we can calculate the importance value of each node and locate the hubs. Profiting from both local and global features of the nodes and the multi-information fusion of human brain biosignals, the experiment results show that this method can detect the brain hubs more accurately and reasonably compared with other methods. Furthermore, the proposed location method is used in impaired brain hubs connectivity analysis of schizophrenia patients and the results are in agreement with previous studies.


Interstitial fluid pressure: A novel biomarker to monitor photo-induced drug uptake in tumor and normal tissues.
Low-dose photodynamic therapy PDT (photoinduction) can modulate tumor vessels and enhance the uptake of liposomal cisplatin (Lipoplatin®) in pleural malignancies. However, the photo-induction conditions must be tightly controlled as overtreatment shuts down tumor vessels and enhances normal tissue drug uptake. In a pleural sarcoma and adenocarcinoma rat model (n = 12/group), we applied photoinduction (0.0625 mg/kg Visudyne®, 10 J/cm2 ) followed by intravenous Lipoplatin® (5 mg/kg) administration. Tumor and normal tissue IFP were assessed before and up to 1 hour following photoinduction. Lipoplatin® uptake was determined 60 minutes following photoinduction. We then treated the pleura of tumor-free minipigs with high dose photodynamic therapy (PDT) (0.0625 mg/kg Visudyne®, 30 J/cm2 , n = 5) followed by Lipoplatin (5 mg/kg) administration. In rodents, photoinduction resulted in a significant decrease of IFP (P < 0.05) in both tumor types but not in the surrounding normal lung, equally exposed to light. Also, photoinduction resulted in a significant increase of Lipoplatin® uptake in both tumor types (P < 0.05) but not in normal lung. Tumor IFP variation and Lipoplatin® uptake fitted an inverted parabola. In minipigs, high dose photodynamic treatment resulted in pleural IFP increase of some animals which predicted higher Lipoplatin® uptake levels. Normal and tumor vasculatures react differently to PDT. Continuous IFP monitoring in normal and tumor tissues is a promising biomarker of vessel photoinduction. Moderate drop in tumor with no change in normal tissue IFP are predictive of specific Lipoplatin® uptake by cancer following PDT. Lasers Surg. Med. 49:773-780, 2017. © 2017 Wiley Periodicals, Inc.


Assessing acute myeloid leukemia susceptibility in rearrangement-driven patients by DNA breakage at topoisomerase II and CCCTC-binding factor/cohesin binding sites.
An initiating DNA double strand break (DSB) event precedes the formation of cancer-driven chromosomal abnormalities, such as gene rearrangements. Therefore, measuring DNA breaks at rearrangement-participating regions can provide a unique tool to identify and characterize susceptible individuals. Here, we developed a highly sensitive and low-input DNA break mapping method, the first of its kind for patient samples. We then measured genome-wide DNA breakage in normal cells of acute myeloid leukemia (AML) patients with KMT2A (previously MLL) rearrangements, compared to that of nonfusion AML individuals, as a means to evaluate individual susceptibility to gene rearrangements. DNA breakage at the KMT2A gene region was significantly greater in fusion-driven remission individuals, as compared to nonfusion individuals. Moreover, we identified select topoisomerase II (TOP2)-sensitive and CCCTC-binding factor (CTCF)/cohesin-binding sites with preferential DNA breakage in fusion-driven patients. Importantly, measuring DSBs at these sites, in addition to the KMT2A gene region, provided greater predictive power when assessing individual break susceptibility. We also demonstrated that low-dose etoposide exposure further elevated DNA breakage at these regions in fusion-driven AML patients, but not in nonfusion patients, indicating that these sites are preferentially sensitive to TOP2 activity in fusion-driven AML patients. These results support that mapping of DSBs in patients enables discovery of novel break-prone regions and monitoring of individuals susceptible to chromosomal abnormalities, and thus cancer. This will build the foundation for early detection of cancer-susceptible individuals, as well as those preferentially susceptible to therapy-related malignancies caused by treatment with TOP2 poisons.


[The expression of insulin signal transduction molecules and islet alpha cell insulin resistance].
To study the changes of insulin signal transduction molecules in islet alpha cells in high-fat-diet plus beta cell-deleting rat models and its underlying mechanism. Thirty SD rats were randomly divided into 2 equal groups and fed with high-fat-diet (HF group) or normal diet (normal control group, NC group) respectively. At the end of twenty-week feeding, the fasting serum insulin (Ins), glucagon (Glc), free fatty acid (FFA), and triglyceride (TG were measured. The glucose infusion rate (GIR) was measured by using euglycemic hyperinsulinemia clamp to evaluate the peripheral insulin resistance. At the same time, large dose streptozocin (100 mg/kg) was injected so as to establish beta cell-deleting rat models, i.e., HF-B group (n = 8) and NC-B group (n = 8). Five days later, the rats of the HF-B and NC-B subgroups were sacrificed, and the pancreatic islets were isolated and collected. The expression of Glc, insulin receptor substrate-1 (IRS-1), IRS-2, and phosphatidylinositol-3-kinase (PI3K) gene in the islets were detected by RT-PCR. (1) The serum FFA, insulin and Glc concentrations of the HF group were 508 (394 - 622) micromol/L, 23.7 (14.0 - 33.4) mIU/L, and 345 (298.6 - 391.4) pg/ml respectively, all significantly higher than those of the NC group [325 (240 - 410) micromol/L, 11.5 (3.6 - 19.4) mIU/L, 256 (226.4 - 285.6) pg/ml; respectively, all P < 0.05]. The GIR of the HF group was 5.25 mgxmin(-1)xkg(-1) +/- 1.2 mgxmin(-1)xkg(-1), significantly lower than that of the NC group (13.6 mgxmin(-1)xkg(-1) +/- 1.7 mgxmin(-1)xkg(-1), P < 0.01)). (2) The gene expression of Glc of the HF-B subgroup was significantly higher than that of the NC-B subgroup by 34.2% +/- 2.1%. In contrast, the expression of IRS-2, and PI3K of the HF-B subgroup was significantly lower than that of the NC-B subgroup by 28.5% +/- 1.8% and 21.3% +/- 1.6% respectively (both P < 0.01). (3) The plasma FFA concentration was asignificantly negatively correlated with GIR (r = -0.675, P < 0.05) and IRS-2 gene expression in islet alpha cells (r = -0.458, P < 0.05) in the HF-B group. High-fat-diet feeding plus beta cell-deleting rat model shows an impaired expression of insulin signal transduction molecules in islet alpha cells which may relate with the increased plasma FFA concentration.


Arteriovenous malformation: a 22-year angiographic follow-up.
A case is reported of an unoperated giant arteriovenous malformation with a progressive deterioration ending in a severe dementia and invalidism. Angiographic documentation is over a 22 year interval. The presentation, diagnosis and treatment of this disease are discussed. It is concluded that early surgical intervention should have a primary role in the management of giant arteriovenous malformation.


Effect of pirfenidone on lung function decline and survival: 5-yr experience from a real-life IPF cohort from the Czech EMPIRE registry.
Pirfenidone, an antifibrotic drug, slows-down the disease progression in idiopathic pulmonary fibrosis (IPF) over 12 months, however limited data on the decline of lung function and overall survival (OS) in real-world cohorts on longer follow-up exists. Of the enrolled Czech IPF patients (n = 841) from an EMPIRE registry, 383 (45.5%) received pirfenidone, 218 (25.9%) no-antifibrotic treatment and 240 (28.5%) were excluded (missing data, nintedanib treatment). The 2- and 5-yrs OS and forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO) were investigated at treatment initiation and 6, 12, 18 and 24 months' follow-up. During a 2-yr follow-up, less than a quarter of the patients progressed on pirfenidone as assessed by the decline of ≥10% FVC (17.0%) and ≥ 15% DLCO (14.3%). On pirfenidone, the DLCO (≥10%) declines at 6, 12, 18 and 24 months' and DLCO (≥15%) declines at 6, 18 and 24 months' follow-up were associated with increased mortality. The DLCO decline showed higher predictive value for mortality than FVC decline. In patients with no-antifibrotics, FVC and DLCO declines were not predictive for mortality. Pirfenidone increased 5-yrs OS over no-antifibrotic treatment (55.9% vs 31.5% alive, P = 0.002). Our study observed the 2-yrs sustained effect of pirfenidone on the decline of lung function and survival in the real-world patient's IPF cohort. DLCO decline of ≥10% shows a potential as a mortality predictor in IPF patients on pirfenidone, and should be routinely evaluated during follow-up examinations.


Aerodynamic levitator for large-sized glassy material production.
Containerless aerodynamic levitation processing is a unique technology for the fabrication of bulk non-crystalline materials. Using conventional aerodynamic levitation, a high reflective index (RI) material (BaTi2O5 and LaO3/2-TiO2-ZrO2 system) was developed with a RI greater than approximately 2.2, which is similar to that of diamond. However, the glass size was small, approximately 3 mm in diameter. Therefore, it is essential to produce large sized materials for future optical materials applications, such as camera lenses. In this study, a new aerodynamic levitator was designed to produce non-crystalline materials with diameters larger than 6 mm. The concept of this new levitator was to set up a reduced pressure at the top of the molten samples without generating turbulent flow. A numerical simulation was also performed to verify the concept.


[Diabetic nephropathy: strategies for prevention].
A cumulative incidence of diabetic nephropathy of 30-35% has been documented after duration of diabetes of at lest 25 years in type 1 diabetes mellitus and 15-25% in type 2 diabetes mellitus. Diabetic Nephropathy has become the leading cause of chronic renal failure. Several strategies has been suggested to prevent renal disease in patients with diabetes mellitus. Two main treatment strategies for primary prevention of diabetic nephropathy are improved glycaemic control and lowering the blood pressure particularly with angiotensing-converting-enzyme inhibitors. Other therapeutics include, lipid-lowering therapy, dietary protein restriction, smoking cessation and aspirin therapy.


Lipoproteins and metabolic control in hypertensive type II diabetics treated with clonidine.
Twenty patients with type II diabetes mellitus and hypertension (WHO stages I and II) participated in a 3-month double-blind cross-over study to evaluate the effects of clonidine (75-300 micrograms daily) on blood pressure, glycemic control and plasma lipoproteins. Already after 1 month's treatment with clonidine the systolic and diastolic blood pressures had decreased, from 168/103 to 161/98 mmHg (p less than 0.01). Fasting blood glucose and HbA1c concentrations were unaffected by 3 months' treatment. Similarly, plasma lipid and lipoprotein concentrations remained unchanged throughout the study (i.e. mean high and low density lipoprotein cholesterol concentrations were 0.89 and 3.87 mmol/l on placebo vs. 0.90 and 3.98 mmol/l on clonidine). Adverse effects were mild and tolerable, and consisted mainly of dryness of the mouth. We conclude that clonidine lowers the blood pressure in patients with type II diabetes without any adverse effects on glycemic control or plasma lipoproteins.


Therapeutic action and the analyst's responsibility.
Models of the psychoanalytic situation can usefully be thought of as fictions. Viewed this way, the models can be understood as narrative structures that shape what we are able to see and how we are able to think about what happens between us and our analysands. Theories of therapeutic action are elements of what can be called a "controlling fiction," mediating between these theories and our very real responsibilities, both to our preferred method and to a suffering patient. This venture into comparative psychoanalysis is illustrated by a discussion of published case material.


Synthesis of nanocomposite materials with controlled structures and optical emissions: application of various methacrylate polymers for CdSe quantum dots encapsulation.
CdSe quantum dots (QDs) were incorporated in polymer films via in situ polymerization using one of the four different monomers having a varied hydrocarbon side chain length, namely, hexyl, lauryl, stearyl, or behenyl methacrylate. This technique resulted in the preparation of a series of the QD-based nanocomposite materials for which laser scanned confocal microscopy imaging revealed a uniform dispersion of nanoparticles within the polymethacrylate matrices. Importantly, the polymer encapsulation of highly luminescent CdSe QDs did not affect their optical properties. The films exhibit the size-quantized optical effects characteristic of QDs. The changes in photoluminescence (PL) intensity of CdSe QDs were investigated as a function of illumination duration in different chemical environments, including the above polymeric matrices and a chloroform solution. Enhancement of the photoluminescence quantum yield for photoactivated QDs in methacrylate polymers was observed. This study of quantum yields of QD-based composites is important for understanding the involvement of surface states of photoactivated QDs as well for identifying ideal polymeric hosts for photoinduced surface passivation.


Flies across the water: genetic differentiation and reproductive isolation in allopatric desert Drosophila.
Between sister species of Drosophila, both pre- and postzygotic reproductive isolation commonly appear by the time a Nei's genetic distance of 0.5 is observed. The degree of genetic differentiation present when allopatric populations of the same Drosophila species exhibit incipient reproductive isolation has not been systematically investigated. Here we compare the relationship between genetic differentiation and pre- and postzygotic isolation among allopatric populations of three cactophilic desert Drosophila: D. mettleri, D. nigrospiracula, and D. mojavensis. The range of all three is interrupted by the Gulf of California, while two species, D. mettleri and D. mojavensis, have additional allopatric populations residing on distant Santa Catalina Island, off the coast of southern California. Significant population structure exists within all three species, but only for allopatric populations of D. mojavensis is significant isolation at the prezygotic level observed. The genetic distances for the relevant populations of D. mojavensis were in the range of 0.12, similar to that for D. mettleri whose greatest D = 0.11 was unassociated with any form of isolation. These observations suggest further investigations of Drosophila populations with genetic distances in this range be undertaken to identify any potential patterns in the relationship between degree of genetic differentiation and the appearance of pre- and/or postzygotic isolation.


Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland.
We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.


Polyamine starvation prolongs the S and G2 phases of polyamine-dependent (arginase-deficient) CHO cells.
This study analyzes the effects of polyamine starvation on cell cycle traverse of an arginase-deficient CHO cell variant (CHO-A7). These cells grow well in serum-free medium, provided that it contains ornithine or polyamines or both. In the absence of ornithine or polyamines or both, the CHO-A7 cells develop severe polyamine deficiency and, as a consequence, grow more slowly. When grown to a stationary phase in the presence of ornithine or putrescine or both, the CHO-A7 cells became arrested in G0/early G1. However, when starved for ornithine and polyamines, they accumulated in the S and G2 phases. Ornithine and polyamine starvation of CHO-A7 cells causes an increase in ornithine decarboxylase activity. When this increase was prevented by treatment with DL-alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, growth was further suppressed, and a greater fraction of cells were found in the S and G2 phases of the cell cycle.


Patients' verbal descriptions of pain and discomfort following orthopaedic surgery.
The concepts of pain and discomfort are poorly differentiated in the literature. This study of 417 post-operative orthopaedic patients examined their use of language to describe pain and also discomfort. Their pain descriptions were assessed for congruence with the widely used McGill pain questionnaire (MPQ). The findings confirmed that there was an overlap in the descriptions of pain and discomfort, but that pain tended to be described as an internal phenomenon, while discomfort was frequently related to environmental stimuli. The use of analogy was commonly used to describe pain. There was considerable use of words not included in the MPQ. This suggests that regional and international variations in vocabulary may render the MPQ unsuitable for indiscriminate use in Anglophone countries. Implications for improving pre-operative information provision and post-operative assessment of pain and discomfort are briefly presented.


Immunoelectron microscopic localization of photoreceptor-specific markers in the monkey retina.
Antibodies for several molecules that function in the visual process were used to localize these molecules in primate rod and cone cells. These antibodies (monoclonal or polyclonal) were prepared against Interphotoreceptor Retinoid-binding Protein (IRBP), S-antigen (S-Ag), opsin, alpha-transducin and also against cyclic GMP (cGMP). Lowicryl-embedded tissues were labeled with secondary antibodies linked to colloidal gold. Although IRBP is predominantly an extracellular protein, the relatively small amount found intracellularly was localized mainly in rods, with little in cones. Opsin, S-Ag and cGMP were found mainly in rod cell outer segments. A polyclonal antiserum raised against transducin-alpha purified from rod outer segments predominantly labeled rod cells, but an antiserum against the carboxyterminal decapeptide of transducin-alpha labeled both rod and cone cells. Thus, most of these specialized molecules are present predominantly in rod cells, confirming major differences in components of the visual cycle in rods and cones.


Lsd1, a metabolic sensor of environment requirements that prevents adipose tissue from aging.
Understanding development and maintenance of beige adipocytes provide exciting insights in establishing novel therapies against obesity and obesity-associated disorders. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser required for differentiation and function of adipocytes. Lsd1 is involved in early commitment of preadipocytes, but dispensable for terminal differentiation of white adipose tissue (WAT). In mature adipocytes, Lsd1 responds to different environmental stimuli to alter metabolic function and enable proper thermogenic and oxidative response. Exposure to cold leads to Lsd1 upregulation and subsequent beiging of WAT. Oppositely, Lsd1 levels decline during aging resulting in a conversion of beige into white adipocytes, associated with loss of thermogenic properties of WAT. Lsd1 maintains beige adipocytes by controlling the expression of the nuclear receptor peroxisome proliferator-activated receptor α. In summary, our studies not only provided insights into the mechanism of age-related beige-to-white adipocyte transition, but also established Lsd1 as a sensor that enables thermogenic response in WAT.


Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion.
Adaptation of the organism to potassium (K+) deficiency requires precise coordination among organs involved in K+ homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K+ retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na+/Cl- cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K+ restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4LPax8/LC1 ) mice exhibited severe hypokalemia and urinary K+ wasting. Notably, expression of the ROMK K+ channel did not change in the distal convoluted tubule and decreased slightly in the cortical/medullary collecting duct, whereas BK channel abundance increased in principal cells of the connecting tubule/collecting ducts. However, K+ restriction also enhanced ENaC expression in Nedd4LPax8/LC1 mice, and treatment with the ENaC inhibitor, benzamil, reversed excessive K+ wasting. Moreover, K+ restriction increased WNK1 and WNK4 expression and enhanced SPAK-mediated NCC phosphorylation in Nedd4LPax8/LC1 mice, with no change in total NCC. We propose a mechanism in which NEDD4-2 deficiency exacerbates hypokalemia during dietary K+ restriction primarily through direct upregulation of ENaC, whereas increased BK channel expression has a less significant role. These changes outweigh the compensatory antikaliuretic effects of diminished ROMK expression, increased NCC phosphorylation, and enhanced WNK pathway activity in the distal convoluted tubule. Thus, NEDD4-2 has a crucial role in K+ conservation through direct and indirect effects on ENaC, distal nephron K+ channels, and WNK signaling.


[Frequency, localization and associated disorders in urinary calculi. Analysis of 1671 autopsies in urolithiasis].
In the area of Rügen-Stralsund a maximum value of urolithiasis and cholelithiasis was found. In 27,133 autopsies the frequency of urolithiasis was 6%. Obesity, hypertension and diabetes mellitus may increase the tendency of cholelithiasis patients to develop additional urolithiasis. Ureteral and urinary bladder calculi are more frequently among male patients. In cases with benign prostatic hyperplasia the incidence of urolithiasis was not higher than in female patients. In the autopsy material multiple calculi and bilateral cases occur more frequently. Hypertension and increased heart weight did occur more frequently in patients suffering from oxalate lithiasis. Some of the calculi may develop in the terminal age of life.


Efficacy of Buqi Huoxue Decoction Combined with Cardiac Rehabilitation Nursing after Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction and Its Influence on Prognosis.
To investigate the efficacy of the application of Buqi Huoxue Decoction combined with cardiac rehabilitation nursing for patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its influence on the prognosis. 120 STEMI patients undergoing PCI were randomly divided into control group, cardiac care group, traditional Chinese medicine and western medicine group (TCM + WM group), and comprehensive treatment group. The control group was treated with a conventional antiplatelet therapy. On the basis of the control group, the cardiac care group was combined with cardiac care treatment. The TCM + WM group was combined with Buqi Huoxue Decoction, and the comprehensive treatment group was combined with cardiac rehabilitation care and Buqi Huoxue Decoction. The total clinical effective rate, readmission rate, and adverse reaction rate of the four groups were measured. Moreover, the myocardial injury markers (creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), and α-Hydroxybutyrate dehydrogenase (α-HBDH)), vascular endothelial function indexes (endothelin (ET-1) and vascular endothelial growth factor (VEGF)), cardiac function indexes (left ventricular ejection fraction (LVEF), left ventricle shortening rate (LFS), left ventricular end diastolic diameter (LVEDd), and left ventricular end systolic diameter (LVESd)), and QOL quality of life score (appetite, spirit, sleep, fatigue, and daily life) were measured. The total effective rate of comprehensive treatment group was obviously increased versus to the control group and cardiac care group. The CK-MB, cTnI, α-HBDH, ET-1, LVEDd, and LVESd levels and SAS and SDS scores in the four groups were decreased, and VEGF, LVEF, and FS levels and QOL quality of life scores were increased after treatment. Moreover, the comprehensive treatment group has more significant changes than the other three groups. The readmission rate in comprehensive treatment group was significantly lower than the other three groups, and the difference in the incidence of adverse reactions in the four groups was not statistically significant. Buqi Huoxue Decoction combined with cardiac rehabilitation after PCI has a significant clinical effect on STEMI patients with PCI postoperative treatment, which can effectively reduce myocardial injury, improve the patient's cardiac function and vascular endothelial function, and improve the patient's quality of life, which can better improve the prognosis of patients.


Results in displaced radial neck fractures in children. Metaizeau technique versus arthrotomy.
The aim of the present article is to ascertain the differences between two surgical treatments commonly used in displaced radial neck fractures in children. We report the retrospective results of 20 displaced radial neck fractures with > 30 degrees of tilt (Judet grades 3-4) in children aged between 7 and 14 years treated with closed intramedullary pinning according to the Metaizeau technique (6 cases) or with arthrotomy and pinning (14 cases). Sex distribution was 14 girls and 6 boy. The average follow-up was 43 months. We found no relationship between delay in the surgical treatment and functional results. On the other hand, a relationship between residual final tilt and poorer functional results appears. The Metaizeau technique produced better results and fewer complications than arthrotomy and pinning, and, in our opinion, is the treatment of choice in this type of fracture.


Debridement versus re-attachment of acetabular labral tears: A review of the literature and quantitative analysis.
We have reviewed the current literature to compare the results of surgery aimed to repair or debride a damaged acetabular labrum. We identified 28 studies to be included in the review containing a total of 1631 hips in 1609 patients. Of these studies 12 reported a mean rate of good results of 82% (from 67% to 100%) for labral debridement. Of the 16 studies that reported a combination of debridement and re-attachment, five reported a comparative outcome for the two methods, four reported better results with re-attachment and one study did not find any significant difference in outcomes. Due to the heterogeneity of the studies it was not possible to perform a meta-analysis or draw accurate conclusions. Confounding factors in the studies include selection bias, use of historical controls and high rates of loss of follow-up. It seems logical to repair an unstable tear in a good quality labrum with good potential to heal in order potentially to preserve its physiological function. A degenerative labrum on the other hand may be the source of discomfort and its preservation may result in persistent pain and the added risk of failure of re-attachment. The results of the present study do not support routine refixation for all labral tears.


Barriers and prospects of India's conditional cash transfer program to promote institutional delivery care: a qualitative analysis of the supply-side perspectives.
Under the National Health Mission (NHM) of India, Janani Suraksha Yojana (JSY) offers conditional cash transfer and support services to pregnant women to use institutional delivery care facilities. This study aims to understand community health workers' (ASHAs) and program officials' perceptions regarding barriers to and prospects for the uptake of facilities offered under the JSY. Fifty in-depth interviews of a purposively selected sample of ASHAs (n = 12), members of Village Health and Sanitation Committees (n = 11), and officials at different tiers of healthcare facilities (n = 27) were conducted in three Indian states. The data were analyzed thematically using ATLAS.ti software. Although the JSY has triggered considerable advancement on the Indian maternal and child health front, there are several barriers to be resolved pertaining to i) delivering quality care at health-facility; ii) linkages between home and health-facility; and iii) the community/household context. At the facility level, respondents cited an inability to treat birth complications as a barrier to JSY uptake, resulting in referrals to other (mostly private) facilities. Despite increased investment in health infrastructure under the program, shortages in emergency obstetric-care facilities, specialists and staff, essential drugs, diagnostics, and necessary equipment persisted. Weaker linkages between various vertical (standalone) elements of maternal and primary healthcare programs, and nearly uniform resource allocation to all facilities irrespective of caseloads and actual need also constrained the provision of quality healthcare. Barriers affecting the linkages between home and facility arose mainly due to the mismatch between the multiple demands and the availability of transport facilities, especially in emergency situations. Regarding community/household context, several socio-cultural issues such as resistance towards the ASHA's efforts of counselling, particularly from elderly family members, often adversely affected people's decision to seek healthcare. Adequate interventions at the community level, capacity building for healthcare providers, and measures to address underlying structural and systemic barriers are needed to improve the uptake of institutional maternal healthcare.


Pavlovian discrimination in rats using voluntary exposure to a lithium chloride procedure.
In a conditioned taste aversion (CTA) procedure, the consumption of a flavor is followed by the administration of a toxin (e.g. lithium chloride, LiCl), resulting in the future avoidance of the flavor. CTA studies typically make use of forced-exposure paradigms where a volume of the toxin dependent upon the weight of the animal is injected. The use of forced paradigms can be problematic when extended training is required, such as in stimulus discrimination training involving similar flavors, since the animals can be exposed to a high amount of the toxin. In the present study we confirmed the viability of an alternative voluntary-exposure paradigm that more closely mimics natural conditions and is more considerate of the welfare of the animals as a useful tool for investigating discrimination training. In three experiments, rats received free access to either a flavor (sucrose in Experiments 1a and 1b, and saccharin in Experiment 2) or a compound of the flavor mixed with LiCl. The presence of LiCl in the compound induced post-consumption illness. Rats acquired an aversion to the flavor + LiCl compound, thus reducing both their consumption of, and exposure to, LiCl, and gradually increased their consumption of the flavor alone. The present paradigm is more similar to natural conditions than the forced-exposure paradigm as it allows the animals to experience a direct relationship between the amount of the flavor consumed and the magnitude of the illness induced by the toxin.


Determinants of quality, latency, and amount of Stack Overflow answers about recent Android APIs.
Stack Overflow is a popular crowdsourced question and answer website for programming-related issues. It is an invaluable resource for software developers; on average, questions posted there get answered in minutes to an hour. Questions about well established topics, e.g., the coercion operator in C++, or the difference between canonical and class names in Java, get asked often in one form or another, and answered very quickly. On the other hand, questions on previously unseen or niche topics take a while to get a good answer. This is particularly the case with questions about current updates to or the introduction of new application programming interfaces (APIs). In a hyper-competitive online market, getting good answers to current programming questions sooner could increase the chances of an app getting released and used. So, can developers anyhow, e.g., hasten the speed to good answers to questions about new APIs? Here, we empirically study Stack Overflow questions pertaining to new Android APIs and their associated answers. We contrast the interest in these questions, their answer quality, and timeliness of their answers to questions about old APIs. We find that Stack Overflow answerers in general prioritize with respect to currentness: questions about new APIs do get more answers, but good quality answers take longer. We also find that incentives in terms of question bounties, if used appropriately, can significantly shorten the time and increase answer quality. Interestingly, no operationalization of bounty amount shows significance in our models. In practice, our findings confirm the value of bounties in enhancing expert participation. In addition, they show that the Stack Overflow style of crowdsourcing, for all its glory in providing answers about established programming knowledge, is less effective with new API questions.


Lower Prevalence of Human Papillomavirus in Head and Neck Squamous Cell Carcinoma in Middle Eastern Population: Clinical Implications for Diagnosis and Prevention.
Introduction Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The prevalence of human papillomavirus (HPV) in HNSCC varies across regions. Objective This study aimed to determine the prevalence of high-risk HPV (hrHPV) among patients with HNSCC in the Middle East region. Methods Samples from patients with oropharyngeal or laryngeal lesions who underwent biopsy or resection at a tertiary care hospital from 2010 to 2015 were collected. Those confirmed as squamous cell carcinoma (SCC) on histopathology were identified as cases (n = 61), whereas benign lesions were used as controls (n = 83). Immunohistochemistry (IHC) for p16, p53, Ki-67, and in situ hybridization (ISH) for hrHPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66 were performed on all cases. Results A total of 154 cases were studied: 61 squamous cell cancers (cases), 83 benign lesions (control), and 10 dysplasia specimens. Among the cases, only five (8.6%) were positive for hrHPV, whereas only one control specimen tested positive. The SCC group had higher mean age, male sex, and history of cigarette smoking and alcohol usage. Among the hrHPV-positive SCC cases, 80% had a tumor in the oropharyngeal region. All hrHPV-positive cases were positive for p16 and p53 immunostains. Conclusion Among HNSCC cases, hrHPV was detected at a lower rate compared to other regions of the world. This study suggests that hrHPV plays a minor role in the pathogenesis of HNSCC in this region, compared to tobacco use and alcohol consumption.


Characterization of bovine adenovirus type 3 E1 proteins and isolation of E1-expressing cell lines.
Like human adenovirus type 5 (HAV5), bovine adenovirus type 3 (BAV3) early region 1 (E1) consists of E1A and E1B transcriptional units. In order to characterize BAV3 E1 proteins and to isolate a cell line of bovine origin that expresses BAV3 E1, polyclonal antibodies specific to E1A, E1B-157R, and E1B-420R were raised in rabbits. BAV3 E1A, E1B-157R, and E1B-420R were identified as 40, 17, and 47 kDa proteins, and had a half-life of 45-60 min, and 4-6 and 4-6 h, respectively. It appeared that E1A and E1B-157R were phosphorylated at the serine/threonine residues, whereas, E1B 420R was phosphorylated at both the serine/threonine and tyrosine residues. Three cell lines, MDBK-221 (Madin Darby bovine kidney (MDBK) transfected with BAV3 E1), FBK-34 (primary fetal bovine kidney (FBK) cells transfected BAV3 E1), and FBRT-HE1 (bovine fetal retinal (FBRT) cells transfected with HAV5 E1) were isolated and characterized for E1 expression. FBK-34 or FBRT-HE1 supported the replication of an E1A-deleted BAV3 (BAV3DeltaE1AE3) to approximately 1-2 x 10(8) PFU/ml, whereas, the virus titers in MDBK-221 were approximately 10(7) PFU/ml. These cell lines will be useful in generating and growing BAV3 E1-deleted recombinants, and also for studying E1 protein interactions with a number of cellular and/or viral proteins.


Determination and identification of hydrophilic and hydrophobic arsenic species in methanol extract of fresh cod liver by RP-HPLC with simultaneous ICP-MS and ESI-Q-TOF-MS detection.
The present study was focused on the determination and identification of arsenic species in methanolic extracts of cod liver. Arsenic species were fractionated and the fractions analysed by RP-HPLC-ICP-MS coupled with ESI-Q-TOF-MS. The total concentration of arsenic in the fresh cod liver was analysed by ICP-MS to be 1.53±0.02 mg As kg(-1)w.w. and the extraction recovery was ca. 100% and the column recovery >93%. Besides polar inorganic and methylated arsenic species (>70%) more hydrophobic arsenic-containing fatty acids and hydrocarbons occurred. Based on the mass spectrometric data proposals for molecular structures were elaborated for 20 of the organic As species included 10 arsenic-containing fatty acids (AsFA) and an arsenic-containing hydrocarbon (AsHC) mentioned for the first time in fresh cod liver. Arsenobetaine was found as main water-soluble arsenic compound in cod liver followed by higher molecular mass arsenic-containing fatty acids and hydrocarbons.


Frequency of 16S rRNA Methylase and Aminoglycoside-Modifying Enzyme Genes among Clinical Isolates of Acinetobacter baumannii in Iran.
Multidrug-resistant Acinetobacter baumannii (MDR-AB) is an important nosocomial pathogen which is associated with significant morbidity and mortality, particularly in high-risk populations. Aminoglycoside-modifying enzymes (AMEs) and 16S ribosomal RNA (16S rRNA) methylation are two important mechanisms of resistance to aminoglycosides. The aim of this study was to determine the prevalence of 16S rRNA methylase (armA, rmtA, rmtB, rmtC, and rmtD), and the AME genes [aac(6')-Ib, aac(3)-I, ant(3'')-I, aph(3')-I and aac(6')-Id], among clinical isolates of A. baumannii in Tehran, Iran. Between November 2015 to July 2016, a total of 110 clinical strains of A. baumannii were isolated from patients in two teaching hospitals in Tehran, Iran. Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute guidelines. The presence of genes encoding the AMEs and 16S rRNA methylases responsible for resistance was investigated by multiplex polymerase chain reaction. The results showed that colistin was an effective antibiotic and could be used as a last-resort treatment of infections caused by MDR-AB. The resistance rate to aminoglycosides were 100%, 96.36% and 90.9% for tobramycin, gentamicin and amikacin, respectively. In this study, AME genes of aac(6')-Ib, aac(3)-I and ant(3'')-I were most prevalent among the isolated strains. Markedly high resistance to tobramycin, gentamicin and amikacin was noted in current study. Our results suggested that modifying enzyme genes in conjunction with methylation of 16S rRNA might contribute to aminoglycoside resistance induced in vivo in A. baumannii. Further studies are required to determine the prevalence of the aminoglycoside resistance genes in other hospitals of Iran.


Organizational determinants of outpatient substance abuse treatment duration in women.
Longer treatment duration has consistently been related to improved substance use outcomes. This study examined how tailored women's programming and organizational characteristics were related to duration in outpatient substance abuse treatment in women. Data were from two waves of a national outpatient substance abuse treatment unit survey (n = 571 in 1999/2000, n = 566 in 2005). Analyses were conducted separately for methadone and nonmethadone programs. Negative binomial regressions tested associations between organizational determinants, tailored programming, and women's treatment duration. Of the tailored programming services, childcare was significantly related to longer duration in the nonmethadone programs, but few other organizational factors were. Tailored programming was not associated to treatment duration in methadone programs, but ownership, affiliation, and accreditation were related to longer duration. Study findings suggest evidence for how external relationships related to resources, treatment constraints, and legitimacy may influence women's treatment duration. Methadone programs may be more vulnerable to external influences.


Precision active pharmaceutical ingredients are the goal.
Understanding and exploiting molecular mechanisms in biology is central to chemical biology. Chemical biology studies of biological macromolecules are now in a perfect continuum with molecular level and nanomolecular level mechanistic studies involving whole organisms. The potential opportunity presented by such studies is the design and creation of genuine precision active pharmaceutical ingredients (APIs; including DNA, siRNA, smaller-molecule bioactives) that demonstrate exceptional levels of disease target specificity and selectivity. This article covers the best of my personal and collaborative academic research work using an organic chemistry and chemical biology approach towards understanding biological molecular recognition processes, work that appears to be leading to the generation of novel precision APIs with genuine potential for the treatments of major chronic diseases that afflict globally.


Gold nanoparticle superlattices as functional solids for concomitant conductivity and SERS tuning.
Mercaptosuccinic acid protected gold nanoparticles (Au@MSA) self assemble to form superlattice (SL) crystals at the air-water interface. These have been used for gas adsorption. The current-voltage (I-V) characteristics of the SL film with embedded SL crystals, obtained by four probe measurements, show Ohmic conduction. The conductance observed was proportional to the polarizability of the adsorbed gases. The current through the SL decreases on adsorption of the gas along with decrease in the SERS intensity of a probe molecule from the crystals. We rationalise our observation of the linear dependence of the conductance on the polarizability of the adsorbed gas using a simple model calculation. Variation of the conductance may be useful in designing electrical switches operating at the nanometre length scales.


Pentoxifylline promotes development of murine colon adenocarcinoma-derived metastatic tumors in liver.
Pentoxifylline is commonly used in the treatment of peripheral vascular diseases. It improves microcirculatory flow and tissue perfusion. Moreover, pentoxifylline displays some immunomodulatory properties that presumably might affect the anticancer response. Therefore, the aim of the present study was to evaluate the influence of pentoxifylline on tumor development. Balb/c mice were injected with murine colon adenocarcinoma C-26 cells intravenously, into the vena portae, and divided into two groups. Mice from the experimental groups received daily intraperitoneal injections of pentoxifylline (30 mg/kg) while the controls were injected with 0.9% NaCl. Two weeks after C-26 cell inoculation mice were sacrificed and autopsy was performed. It was found that the livers of control animals revealed only several small tumor foci, whereas the livers of pentoxifylline-treated mice displayed numerous cancerous outgrowths. The mean liver weight in pentoxifylline group was 2.21+/-0.62 g as compared to 1.36+/-0.15 g in controls (P=0.004). Moreover, the influence of pentoxifylline on murine and human cell line proliferation in vitro was evaluated. It has been observed that pentoxifylline, at pharmacologically achievable concentrations, stimulated the proliferation of murine (C-26) and human (CaSki, U-937) cell lines. However, it did not stimulate human melanoma (WM-35) cell proliferation. Since there has been no evidence so far that pentoxifylline may promote tumor progression, it is still considered to be a safe drug. Moreover, some beneficial properties of pentoxifylline, which could be useful in cancer treatment, have been reported and a few clinical trials with oncological patients have been performed. Surprisingly, our study revealed that pentoxifylline significantly promoted C-26-derived metastatic tumor growth in liver. Although this model might be unique in its sensitivity to tumor-promoting effects of pentoxifylline, it cannot be excluded that similar effects might occur in some cases of tumors developing in humans. Such effects could be relevant, since the stimulatory influence of pentoxifylline on proliferation does not appear to be species- or tissue-specific.


[Abdominal pain and flatulence. Intestinal and pulmonary tuberculosis. IgG kappa paraproteinemia].
A 21-year-old woman suffered from cramplike abdominal pain, flatulence and occasional diarrhoea for about one year. Over the past few weeks the abdominal symptoms exacerbated, besides productive cough and subfebrile temperatures developed. Coloscopy revealed two isolated, short ulcers in the proximal colon. The histological examination of the biopsies taken from these ulcers indicated granulomatous inflammation. Moreover small acinar infiltrates in both pulmonary apices were visualized. The findings in this patient originating from Turkey were suspicious for intestinal and pulmonary tuberculosis. Though sensitive methods were used (Ziehl-Neelson stam, amplified M. tuberculosis direct test, a polymerase chain reaction) direct tests allowed no detection of mycobacteria. Antituberculous therapy was initiated on a probatory basis to which the patient responded well and promptly. The diagnosis was confirmed by culture results: M. tuberculosis was grown from colonic biopsies, morning sputa and bronchioalveolar lavage.


Pre-Existing Mesh at the Hiatus in Revisional Surgery Does Not Result in Increased Morbidity: A Case-Control Evaluation.
Mesh is sometimes used to reinforce the hiatus during primary and reoperative fundoplication. This is a controversial practice as it is not clear that this leads to a decreased rate of failure of the hiatal closure, and concerns about morbidity related to the presence of mesh in this location exist. One of these concerns is that if reoperation is ever required (fundoplication herniates through the hiatus, for example), revisional surgery would be significantly more difficult and associated with a higher rate of morbidity than if mesh had not been placed at the hiatus in a previous procedure. A retrospective review was conducted of prospectively collected data on 104 patients to undergo surgery for a failed fundoplication between 2011 and 2015. Fourteen patients (13.5%) had previous operations where mesh had been placed at the hiatus and underwent a subsequent revisional procedure. Procedures performed were reoperative fundoplication and Roux-en-Y gastric bypass as a salvage procedure for a failed fundoplication, especially in the setting of obesity. These 14 cases were matched 1:2 with randomly selected control patients from the database who underwent revisional surgery in whom mesh had not been placed at the original operation. Cases and controls were paired based on the number of previous revision attempts and operation type. Perioperative outcomes were compared. There was no statistically significant difference in 30-day morbidity, readmission, operative time, or length of hospital stay. In this retrospective case-control evaluation, mesh at the hiatus did have an impact on morbidity or operative time.


Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus.
Perampanel is the latest approved antiepileptic drug in focal and generalized epilepsies and has a distinct and selective mode of action on AMPA-receptors. Several thousand patients have received perampanel within randomized placebo-controlled trials, open-label extension trials and post-marketing observational studies. Significant median partial-onset seizure reduction rates of 23% for 4 mg/day, 26-31% for 8 mg/day and 18-35% for 12 mg/day were reported. Likewise 50 percent responder rates were 29% for 4 mg/day, 33-38% for 8 mg/day and 34-36% for 12 mg/day. Primary generalized tonic-clonic seizures were reduced by 76.5% (8 mg) vs 38.4% (placebo) in a recent controlled trial. Overall, perampanel is well tolerated and the main adverse events are dizziness, somnolence and fatigue. There are also anecdotal reports on use in progressive myoclonic epilepsies and status epilepticus. Perampanel will likely remain an important, possibly broad-spectrum AED with a significant market share, especially in patients with drug-refractory epilepsies.


In-situ competition between protamine and fluorochromes for sperm DNA.
In this study we investigated the relationship between the presence of bound protamine on mouse and human sperm DNA and the level of chromomycin A3 (CMA3) and 4'6-diamidino-2-phenylindole (DAPI) fluorescence. This was accomplished by performing a competition assay between salmon protamine and fluorochromes on decondensed spermatozoa that had their nuclear proteins extracted and were fixed on slides. Various concentrations (0, 0.005, 0.0225, 0.05, 0.225, 0.5 and 5 mg/ml) of salmon protamine were added to either the CMA3 or DAPI staining solutions. Fluorescence emission measurements of stained sperm nuclei were then performed using a microfluorometer. When the treated decondensed sperm heads were stained with either CMA3 or DAPI all spermatozoa were found to fluoresce intensely. The addition of protamines to the spermatozoa led to an elimination of CMA3 fluorescence, while the intensity of DAPI staining was decreased to approximately 50% at the highest concentrations of protamine. The addition of increasing amounts of salmon protamine also induced the sperm nuclei to regain their initial condensed appearance. This study shows that protamine retains a strong affinity for sperm DNA in situ and that CMA3 fluorescence is a strong indicator of the protamination state of spermatozoa.


Impaired bactericidal activity of cord sera against Salmonella strains.
Weaker bactericidal activity of cord sera against Salmonella bacilli was shown in comparison with maternal venous sera. No correlation was found between the bactericidal activity and the levels of complement, immunoglobulins and lysozyme in cord sera. Worthy of notice is detected in these researches specificity of bactericidal action of cord sera.


High-dose cyclophosphamide, etoposide and BCNU (CVB) with autologous stem cell rescue in malignant lymphomas.
Eighteen patients with malignant lymphoma, 10 non-Hodgkin's and 8 Hodgkin's, were treated with high-dose CVB (cyclophosphamide 4 x 1.5 g/m2, etoposide 4 x 250-400 mg/m2, carmustine 4 x 150-200 mg/m2), followed by autologous peripheral blood stem cells (PBSC, 13 patients) or bone marrow (BM, 5 patients) transplantation. At the time of autograft 6 patients were in complete remission (CR), 3 in partial remission (PR) and 5 in relapse (4 sensitive, 1 resistant), whereas 4 had progressive disease. All CR patients had poor prognostic features at presentation. PBSC were collected at the time of rapid hematologic recovery after intense chemotherapy by means of a cell separator. All patients engrafted. Median time to achieve > or = 0.5 x 10(9)/l polymorphonuclear cells (PMN) and > or = 50 x 10(9)/l platelets was 13 days for both cell types in PBSC autografted patients, versus 20 and 28 days respectively in BM autografted patients. A significant advantage of PBSC over BM was found in terms of time needed to recover either PMN > or = 0.5 and PMN > or = 1 x 10(9)/l (p = 0.01). Autograft-related toxicity consisted mainly of moderate severity interstitial pneumopathy (3 patients), and veno-occlusive disease (1 patient) that resolved completely. Of the 12 patients autografted with detectable disease, 6 (50%) obtained a CR. Seven out of 18 autografted patients (39%) had disease progression within 1 to 5 months of autograft. The projected progression-free survival is over 50% at 4 years and it was significantly longer in patients with sensitive disease than in those with resistant disease (p = 0.01). The efficacy and the low toxicity of CVB suggest that autograft with PBSC may be proposed for the primary treatment of poor prognosis malignant lymphomas.


Aseptic meningitis due to varicella-zoster virus: serum antibody levels and local synthesis of specific IgG, IgM, and IgA.
We used an indirect enzyme immunoassay to describe the evolution of serum levels and the intrathecal production of IgG, IgA, and IgM antibodies to varicella-zoster virus (VZV) in eight patients with a syndrome of acute aseptic meningitis (AAM) and evidence of intrathecal production of VZV-specific IgG antibodies. Four of the eight patients showed no cutaneous zoster while hospitalized. Our results suggested an etiologic relation between VZV and AAM in all cases. Furthermore, we observed some differences in the pattern of evolution of antibodies in serum and cerebrospinal fluid in relation to the presence or absence of cutaneous lesions in our patients. These differences could reflect different pathogenic mechanisms in the spread of VZV to the central nervous system and in the production of the AAM syndrome.


The role of CYP17A1 in prostate cancer development: structure, function, mechanism of action, genetic variations and its inhibition.
Androgens play an important role during the development of both normal prostate epithelium and prostate cancer and variants of genes involved in androgen metabolism may be related to an increased risk of prostate disease. Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a key regulatory enzyme in the steroidogenic pathway; it catalyses both 17α-hydroxylase and 17,20-lyase activities and is essential for the production of both androgens and glucocorticoids. In this review, we focus on the structure and enzymatic activity of CYP17A1 and the mechanism of modulation of CYP17A1 activities. We discuss the relationship between common genetic variations in CYP17A1 gene and prostate cancer risk and the main effects of these variations on the prediction of susceptibility and clinical outcomes of prostate cancer patients. The mechanism of action, the efficacy and the clinical potential of CYP17A1 inhibitors in prostate cancer are also summarized.


[Treatment of four cases of Fanconi anemia by allogeneic hematopoietic stem cell transplantation with low intensity conditional regimen].
Objective: To evaluate the efficiency and safety of low intensity conditional regimen for children with Fanconi anemia (FA) receiving allogenic hematopoietic stem cells transplantation (allo-HSCT). Methods: Four patients diagnosed as Fanconi anemia were enrolled in this study. One patient received HLA-identical sibling donor hematopoietic stem cell transplantation, two patients underwent unrelated donor matched (UD) HSCT, and one patient received unrelated cord blood transplantation. The conditional regimen consisted of Busulfan with low dose of cyclophosphamide. Results: All 4 cases succeeded in allo-HSCT. The median time for neutrophils engraftment was 11(9-15) day, median time to platelets (PLT) engraftment was 12 (8-28) day. One case occurred with grade I of aGVHD, 1 case with hemorrhagic cystitis. No patient happened with hepatic veno-occlusive disease (VOD). Conclusion: Low intensity of conditional regimen is efficient and safe which should be recommended for FA patients with HSCT.


Characterization of a novel RP2-OSTF1 interaction and its implication for actin remodelling.
Retinitis pigmentosa 2 (RP2) is the causative gene for a form of X-linked retinal degeneration. RP2 was previously shown to have GTPase-activating protein (GAP) activity towards the small GTPase ARL3 via its N-terminus, but the function of the C-terminus remains elusive. Here, we report a novel interaction between RP2 and osteoclast-stimulating factor 1 (OSTF1), an intracellular protein that indirectly enhances osteoclast formation and activity and is a negative regulator of cell motility. Moreover, this interaction is abolished by a human pathogenic mutation in RP2. We utilized a structure-based approach to pinpoint the binding interface to a strictly conserved cluster of residues on the surface of RP2 that spans both the C- and N-terminal domains of the protein, and which is structurally distinct from the ARL3-binding site. In addition, we show that RP2 is a positive regulator of cell motility in vitro, recruiting OSTF1 to the cell membrane and preventing its interaction with the migration regulator Myo1E.


Therapeutic Plasma Exchange in Neonates and Infants: Successful Use of a Miniaturized Machine.
Therapeutic plasma exchange (TPE) in neonates and small infants is a treatment method at the forefront that may become a potentially life-saving procedure in a wide array of severe conditions. Indications for TPE in the pediatric population have been mainly derived from adult literature, with neonatal hyperbilirubinemia being the most notable exception. The only alternative to TPE in small pediatric patients is manual blood exchange transfusion, which, however, bears an unacceptably high risk of severe complications. Still, technical issues due to extracorporeal circulation in neonates have burdened TPE so far, since machines developed for adults require a relatively large blood volume to operate. We in this study, describe our preliminary experience of TPE for treating 2 potentially life-threatening conditions in neonatal age. To overcome the aforementioned limitations, plasmapheresis was performed in both cases using a machine specifically designed for patients weighing less than 10 kg.


Comparison Of The I-Gel Supraglottic And King Laryngotracheal Airways In A Simulated Tactical Environment.
When working in a tactical environment there are several different airway management options that exist. One published manuscript suggests that when compared to endotracheal intubation, the King LT laryngotracheal airway (KA) device minimizes time to successful tube placement and minimizes exposure in a tactical environment. However, comparison of two different blind insertion supraglottic airway devices in a tactical environment has not been performed. This study compared the I-Gel airway (IGA) to the KA in a simulated tactical environment, to determine if one device is superior in minimizing exposure and minimizing time to successful tube placement. This prospective randomized cross over trial was performed using the same methods and tactical environment employed in a previously published study, which compared endotracheal intubation versus the KA in a tactical environment. The tactical environment was simulated with a one-foot vertical barrier. The participants were paramedic students who wore an Advanced Combat Helmet (ACH) and a ballistic vest (IIIA) during the study. Participants were then randomized to perform tactical airway management on an airway manikin with either the KA or the IGA, and then again using the alternate device. The participants performed a low military type crawl and remained in this low position during each tube placement. We evaluated the time to successful tube placement between the IGA and KA. During attempts, participants were videotaped to monitor their height exposure above the barrier. Following completion, participants were asked which airway device they preferred. Data was analyzed using Student's t-test across the groups for time to ventilation and height of exposure. In total 19 paramedic students who were already at the basic EMT level participated. Time to successful placement for the KA was 39.7 seconds (95%CI: 32.7-46.7) versus 14.4 seconds (95%CI: 12.0-16.9) for the IGA, p < 0.001. Maximum height exposure of the helmet above a one foot vertical barrier for the KA resulted in 1.42 inches of exposure (95%CI: 0.38-0.63) compared to the IGA with 1.42 inches, 95%CI:0.32-0.74, p = 0.99. On questioning 100% of the participants preferred the IGA device over the KA. In a simulated tactical environment placement of the IGA for airway management was faster than with the KA, but there was no difference in regard to exposure. Additionally, all the participants preferred using the IGA device over the KA.


Physiologic cardiovascular strain and intrinsic wave imaging.
Cardiovascular disease remains the primary killer worldwide. The heart, essentially an electrically driven mechanical pump, alters its mechanical and electrical properties to compensate for loss of normal mechanical and electrical function. The same adjustment also is performed in the vessels, which constantly adapt their properties to accommodate mechanical and geometrical changes related to aging or disease. Real-time, quantitative assessment of cardiac contractility, conduction, and vascular function before the specialist can visually detect it could be feasible. This new physiologic data could open up interactive therapy regimens that are currently not considered. The eventual goal of this technology is to provide a specific method for estimating the position and severity of contraction defects in cardiac infarcts or angina. This would improve care and outcomes as well as detect stiffness changes and overcome the current global measurement limitations in the progression of vascular disease, at little more cost or risk than that of a clinical ultrasound.


Improving Electronic Patient Handoff in an Orthopaedic Residency using the Listrunner© Application.
Miscommunication during shift change and other handoff events is a common source of malpractice claims and patient-care errors. An efficient patient handoff system is imperative to prevent miscommunication. Owning to limitations with our current handoff system and to an ever-increasing reliance on electronic health information, our residency program sought to modernize our handoff method. To improve handoff communication, the HIPAA-compliant application Listrunner© was adopted. Members of the orthopaedic trauma team were oriented to the new application. Change-of-shift patient handoff was transitioned from the current email system to List-runner©. After three months of using the new application, a web-based questionnaire was administered to all members of the care team to assess their experiences, including perceived benefits and limitations of the Listrunner© application. Seventeen orthopaedic resident physicians and three orthopaedic trauma attending physicians completed the survey. While almost half of the respondents were satisfied using email as a checkout tool, more than half of study participants indicated that it lacked security and several users believed there was a need for improvement. Most indicated that Listrunner© was easy to use, improved clinical efficiency, and improved patient care and safety. Seventeen of 20 respondents reported that they would like to continue using Listrunner© as a check-out tool. The Listrunner© application was adopted quickly by our orthopaedic trauma team, whose members opined that the application increased the efficiency and accuracy of handoff when compared to the previous secure email system.


What is the optimal medical management of infertility and minor endometriosis? Analysis and future prospects.
By asking the question 'What is the optimal medical management of infertility and minor endometriosis?', it is assumed that endometriosis has a detrimental effect on fertility. The published data suggest that oocyte dysfunction may contribute to infertility associated with endometriosis. This is expressed as a reduction in fertilization and implantation rates; implantation rates to a lesser extent, though still significant. Other evidence for oocyte dysfunction exists, not all of which is consistent. Suppression of ovulation and menstruation to treat endometriosis-associated infertility is not effective. However, ovulation induction, perhaps with intrauterine insemination, does result in pregnancy rates higher than in control cycles, while stimulated IVF success rates are equivalent to those of other diagnostic groups. For the future, angiogenesis is critical to the support of endometriotic deposits and targeted therapies are promised; their role in improving fertility has not yet been explored.


Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38.
Monoclonal antibodies have the potential to target therapy for high-grade gliomas. Monoclonal antibody 8H9 is specific for membrane protein B7H3 and is reactive with most human high-grade gliomas. We tested the 8H9scFv-PE38 recombinant Pseudomonas immunotoxin in a preclinical model of high-grade glioma. The half maximal inhibitory concentration (IC(50)) of 8H9scFv-PE38 in vitro was determined using glioblastoma cell lines U87 and U251. Maximum tolerated infusion dose of 8H9scFv-PE38 following interstitial infusion to the striatum and pons was defined using athymic rats. Maximum tolerated infusion dose of 8H9scFv-PE38 or PBS control were interstitially delivered to athymic rats xenografted with U87 in the striatum or brain stem. Radiographic response and survivals were measured and compared between treatment groups. The in vitro IC(50) of 8H9scFv-PE38 for U87 was 1,265 ng/mL and, for U251, 91 ng/mL. The maximum tolerated infusion doses of interstitially infused 8H9scFv-PE38 to the striatum and brain stem were 0.75 and 1.8 mug, respectively. For rats harboring intracranial U87 xenografts, infusion of 8H9scFv-PE38 increased mean survival (striatum, 43.4 versus 24.6 days; brain stem, 80.6 versus 45.5 days; n = 28 total) and produced three long-term survivors past 120 days. None of the 14 placebo-treated animals survived >54 days. Tumors also showed volumetric response to infusion of 8H9scFv-PE38 by magnetic resonance imaging. Interstitial infusion of 8H9scFv-PE38 shows potential for the treatment of hemispherical and brain stem glioma. Mol Cancer Ther; 9(4); 1039-46. (c)2010 AACR.


Developmental influences on adult ovarian hormonal function.
The hypothesis is advanced that levels of ovarian hormonal function in adult women are associated with the tempo of growth and maturation in childhood and adolescence. Empirical data are presented documenting a correlation between menarcheal age and adult ovarian hormonal function both within and between populations. It is noted that this relationship is compatible with current understanding of the mechanisms underlying pubertal maturation of ovarian hormonal function. Functionally, such a relationship could serve the purpose of modulating adult fecundity to chronic environmental conditions. Alternative hypotheses include the possibility that the relationship is not causal but rather reflects either confounded effects of some common cause or the persistence of acute environmental effects through time. Proper testing of such alternative hypotheses will require longitudinal data on migrant populations, changing environments, or secular trends within populations. The importance of establishing the relationship between development and adult ovarian hormonal function is not limited to issues of fecundity and fertility, but includes other areas of female general and reproductive health. © 1996 Wiley-Liss, Inc.


GPs' experiences with loneliness.
Loneliness has a negative influence on health. General practitioners are confronted with lonely patients in their daily practice, but there is little information about how GPs deal with loneliness. A qualitative study using semistructured interviews with 20 GPs who practise integrative medicine in the Netherlands. There are GPs who never ask patients about loneliness. Others mostly raise the topic indirectly. General practitioners sometimes notice that discussing loneliness brings relief to their patients. Almost all interviewed GPs have feelings of deficiency in their ability to provide health care to lonely patients. A feeling of powerlessness and perceived lack of time are the reasons given to avoid a discussion of loneliness. Loneliness is a widespread phenomenon and a difficult problem according to the GPs interviewed in this study. Discussing loneliness with patients should not be avoided in general practice.


Survivorship care planning in a comprehensive cancer center using an implementation framework.
Cancer survivorship care plans (SCPs) have been recommended to improve clinical care and patient outcomes. Research is needed to establish their efficacy and identify best practices. Starting in 2015, centers accredited by the American College of Surgeons Commission on Cancer must deliver SCPs to patients completing primary cancer treatment with curative intent. We describe how we established routine SCP delivery at the Robert H Lurie Comprehensive Cancer Center in Chicago, Illinois, using the Quality Implementation Framework. We evaluated local practices, gathered clinician and patient stakeholder input, developed customized SCP templates within the electronic health record (EHR), and implemented 2 complementary delivery models. Clinician interviews (n = 41) and survey responses (n = 12), along with input from patients (n = 68) and a patient advisory board (n = 15), indicated support for SCPs and survivorship services. To promote feasible implementation and leverage existing workflows, we harmonized 2 SCP delivery models: integrated care within clinics where patients received treatment, and referral to a centralized survivorship clinic. We are implementing SCP delivery with prominent disease sites and will extend services to survivors of other cancers in the future. We developed four electronic disease-specific SCP templates for breast, colorectal, lung, and prostate cancers and a fifth, generic template that can be used for other malignancies. The templates reduced free-text clinician entry by auto-populating 20% of the fields from existing EHR data, and using drop-down menus for another 65%. Mean SCP completion time is 12 minutes (range, 10-15; n = 64). We designed our framework to facilitate ongoing evaluation of implementation and quality improvement. Funding/sponsorship Robert H Lurie Comprehensive Cancer Center, the Coleman Foundation, and the Lynn Sage Cancer Research Foundation.


Modulation of Methamphetamine-Related Attention Bias by Intermittent Theta-Burst Stimulation on Left Dorsolateral Prefrontal Cortex.
Previous studies have identified the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on cravings of patients with methamphetamine use disorder (MUD). However, the mechanism underlying the treatment effect remains largely unknown. A potential candidate mechanism could be that rTMS over the dorsolateral prefrontal cortex (DLPFC) modulates the attention bias to methamphetamine-related cues. The purpose of this study is therefore to determine the modulation of rTMS on methamphetamine-related attention bias and the corresponding electrophysiological changes. Forty-nine patients with severe MUD were included for analysis. The subjects were randomized to receive the active intermittent theta-burst stimulation (iTBS) or sham iTBS targeting DLPFC for 20 sessions. Participants performed the Addiction Stroop Task before and after the treatment while being recorded by a 64-channel electroencephalogram. Baseline characteristics were collected through the Addiction Severity Index. Post-treatment evaluations showed a reduced error rate in discriminating the color of methamphetamine words in the active iTBS group compared with the sham iTBS group. Following rTMS treatment, we found the significant time-by-group effect for the N1 amplitude (methamphetamine words > neutral words) and P3 latency (methamphetamine words > neutral words). The change of N1 amplitude was positively correlated with cravings in the active group. Moreover, reduced power of neural oscillation in the beta band, manifesting at frontal central areas, was also found in the active group. This study suggests that attention bias and the beta oscillation during the attentional processing of methamphetamine words in patients with MUD could be modulated by iTBS applied to left DLPFC.


Site selection for subtropical thicket restoration: mapping cold-air pooling in the South African sub-escarpment lowlands.
Restoration of subtropical thicket in South Africa using the plant Portulacaria afra (an ecosystem engineer) has been hampered, in part, by selecting sites that are frost prone-this species is intolerant of frost. Identifying parts of the landscape that are exposed to frost is often challenging. Our aim is to calibrate an existing cold-air pooling (CAP) model to predict where frost is likely to occur in the valleys along the sub-escarpment lowlands (of South Africa) where thicket is dominant. We calibrated this model using two valleys that have been monitored during frost events. To test the calibrated CAP model, model predictions of frost-occurrence for six additional valleys were assessed using a qualitative visual comparison of existing treelines in six valleys-we observe a strong visual match between the predicted frost and frost-free zones with the subtropical thicket (frost-intolerant) and Nama-Karoo shrubland (frost-tolerant) treelines. In addition, we tested the model output using previously established transplant experiments; ∼300 plots planted with P. afra (known as the Thicket-Wide Plots) were established across the landscape-without consideration of frost-to assess the potential factors influencing the survival and growth of P. afra. Here we use a filtered subset of these plots (n = 70), and find that net primary production of P. afra was significantly lower in plots that the model predicted to be within the frost zone. We suggest using this calibrated CAP model as part of the site selection process when restoring subtropical thicket in sites that lie within valleys-avoiding frost zones will greatly increase the likelihood of restoration success.


Increasing Mental Health Literacy in Law Enforcement to Improve Best Practices in Policing-Introduction of an Empirically Derived, Modular, Differentiated, and End-User Driven Training Design.
Objective: Law enforcement officers often have contact to persons who show symptoms of mental disorders. Adequately designed training is necessary for developing the best possible practices in policing when coming into contact with mentally ill people, and may help to expand their general knowledge on mental disorders. To achieve a sustainable implementation of training content in daily policing work, the acceptance and proactive integration of methods by the training participants is essential. Method: This study investigates an exemplary modular training curriculum based on a survey with 2,228 German police officers (28.2% female, 71.8% male) concerning their needs and challenges when coming into contact with persons with mental disorders. This empirical end-user driven approach was used to adapt existing training concepts to the current needs and interests of law enforcement personnel in order to maximize compliance. Results: The training program draft includes basic modules which are intended to be of direct interest to all police officers, such as mental disorders with high policing relevance, encountering suicidal patients, (non-directive) communication and de-escalation skills, and mental hygiene in policing. They are arranged in more specialized modules that address specific target group audiences within police forces and the training curriculum provides information about genuine risks and self-protection, trauma sensitivity, and interaction with children and victims among other contents. The self-selectable, modular, and empirically-based continued training program also includes an introduction to local mental health service professionals and networks, trialogue sequences, and situational role play scenarios. Conclusion: Due to frequent contact law enforcement officers have to mentally ill people, improved training designed to maximize knowledge and the integration of trained methods is necessary. Gaining acceptance and proactive support by trainees is ensured through end-user driven implementation of specialized and differentiated up-to-date training programs. Our results showcase how police officers' perspectives on persons with mental illnesses is a main aspect that can and should be used to encourage training course designs.