Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer.
Despite the successful application of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, the treatment efficacy in solid tumors remains unsatisfactory, largely due to the highly immunosuppressive tumor microenvironment and low density of specific tumor antigens. Natural killer group 2 member D (NKG2D) CAR-T cells have shown promising treatment effects on several cancers such as lymphoma and multiple myeloma. However, the application and efficacy of NKG2D-CAR-T cells in gastric cancer (GC) still needs further exploration. This study identified a novel combination immunotherapy strategy with Dickkopf-1 (DKK1) inhibition and NKG2D-CAR-T cells, exerting synergistic and superior antitumor effect in GC. We show that the baseline expression of NKG2D ligands (NKG2DLs) is at low levels in GC tissues from The Cancer Genome Atlas and multiple GC cell lines including NCI-N87, MGC803, HGC27, MKN45, SGC7901, NUGC4, and AGS. In addition, DKK1 inhibition by WAY-262611 reverses the suppressive tumor immune microenvironment (TIME) and upregulates NKG2DL expression levels in both GC cell lines and GC tissues from a xenograft NCG mouse model. DKK1 inhibition in GC cells markedly improves the immune-activating and tumor-killing ability of NKG2D-CAR-T cells as shown by cytotoxicity assays in vitro. Moreover, the combination therapy of NKG2D-CAR-T and WAY-262611 triggers superior antitumor effects in vivo in a xenograft NCG mouse model. In sum, our study reveals the role of DKK1 in remodeling GC TIME and regulating the expression levels of NKG2DLs in GC. We also provide a promising treatment strategy of combining DKK1 inhibition with NKG2D-CAR-T cell therapy, which could bring new breakthroughs for GC immunotherapy.


Feasibility of laparoscopic cholecystectomy with miniaturized instrumentation in 50 consecutive cases.
A new technique utilizing miniaturized (2 mm) instrumentation to perform laparoscopic cholecystectomy (LC) is introduced. The safety and efficacy of this mini-LC were assessed. Fifty consecutive mini-LCs were performed using one 10-mm port and three 2-mm ports (cumulative port size 16 mm). A 2-mm fiberoptic video-laparoscope was placed in the mid-epigastrium through a 2-mm port. A 10-mm umbilical port was then placed under direct visualization, allowing access for standard laparoscopic instruments. Two additional 2-mm ports were placed in the right upper quadrant allowing insertion of grasping instruments. Parameters reviewed included total operative time (OT), postoperative length of stay (LOS), anatomic pathology, complications, and rate of conversion to conventional LC and open cholecystectomy. Results were compared to those of 50 consecutive conventional LCs using two 10-mm and two 5-mm ports (cumulative port size 30 mm). The OT for the mini-LC and conventional LC were 88 +/- 5.9 and 78 +/- 5 minutes (mean +/- SD), respectively, (p = NS), and postoperative LOS for the mini-LC and conventional LC were 1.5 +/- 0. 2 and 1.8 +/- 0.4 days (mean +/- SD), respectively, (p = NS). Of the 50 mini-LC cases, 5 required conversion to conventional LC. One cystic duct leak was detected and successfully treated conservatively; no common bile duct injuries occurred; and no patients required conversion to open cholecystectomy. This study demonstrates the safety and efficacy of minilaparoscopic instruments for the performance of cholecystectomy. The data reveal that this new technique is comparable to conventional LC.


Fertility and Minority: A Study in Two Provinces of Iran Using Matching Estimator Technique.
The main aim of this study was to compare fertility in minor (Sunnah) and major (Shia) religious groups of Iran after matching the two groups by some confounding factors. 12,099 data of population and census survey of Iran in 2011 in two provinces of Guilan and Kurdistan were used in this study. Propensity scoring matching method was used for matching two groups. First confounder variables were found and after that the groups were matched. Principal component analysis was used to make a socioeconomic (SES) variable. At the end, two groups were compared to each other by nearest neighborhood method. Also Poisson regression was used to find the effective factors of fertility. Before using matching method, the results showed that fertility in Kurdistan was higher than Guilan, but after matching, fertility in Guilan was higher. The results of regression model showed that in Guilan, living in urban region, age and level of education had effect on fertility, but in Kurdistan, education, age and SES were effective factors.


Visualization of basilar invagination by computerized tomography.
Computerized tomography was used to visualize bony masses in the posterior fossa in a patient with basilar invagination associated with symptoms of vertebrobasilar insufficiency.


Video-supported analysis of Beggiatoa filament growth, breakage, and movement.
A marine Beggiatoa sp. was cultured in semi-solid agar with opposing oxygen-sulfide gradients. Growth pattern, breakage of filaments for multiplication, and movement directions of Beggiatoa filaments in the transparent agar were investigated by time-lapse video recording. The initial doubling time of cells was 15.7 +/- 1.3 h (mean +/- SD) at room temperature. Filaments grew up to an average length of 1.7 +/- 0.2 mm, but filaments of up to approximately 6 mm were also present. First breakages of filaments occurred approximately 19 h after inoculation, and time-lapse movies illustrated that a parent filament could break into several daughter filaments within a few hours. In >20% of the cases, filament breakage occurred at the tip of a former loop. As filament breakage is accomplished by the presence of sacrificial cells, loop formation and the presence of sacrificial cells must coincide. We hypothesize that sacrificial cells enhance the chance of loop formation by interrupting the communication between two parts of one filament. With communication interrupted, these two parts of one filament can randomly move toward each other forming the tip of a loop at the sacrificial cell.


Do patients who experience episodic tilting or translational sensations in the pitch plane have abnormal sacculo-collic reflexes?
The otolith-collic and otolith-ocular reflexes of patients who experienced episodic tilting or translational sensations in the pitch plane without any other vestibular symptoms were assessed using cervical vestibular evoked myogenic potentials (cVEMP) and ocular vestibular evoked myogenic potentials (oVEMP). Eleven patients (4 men and 7 women, mean age=40.4) were enrolled. All of the patients complained of episodic tilting or translational sensations in the pitch plane. Patients with a medical history of rotatory vertigo, loss of consciousness, head trauma, or symptoms of central nervous dysfunction or proprioceptive dysfunction and those who had been definitely diagnosed with a disease that causes disequilibrium were excluded. All 11 patients underwent cVEMP and caloric tests. Ten patients participated in the oVEMP tests. Seven of the 11 patients exhibited unilateral cVEMP absences, two displayed bilateral cVEMP absences, one demonstrated unilaterally decreased cVEMP, and one displayed normal cVEMP. Concerning oVEMP, 2 of the 10 patients showed unilateral oVEMP absences, 2 displayed bilateral oVEMP absences, 2 exhibited unilaterally decreased oVEMP, and 4 displayed normal oVEMP. All patients exhibited normal bilateral caloric responses. These findings were distinct from the results obtained for patients who experienced episodic lateral tilting sensations in previous studies. While most of the latter patients exhibited abnormal oVEMP, the patients in the present study tended to display abnormal cVEMP. These results suggest that patients with episodic tilting or translational sensations in the pitch plane suffer from saccular dysfunction. We propose "idiopathic otolithic vertigo" as a clinical entity and suggest that it is caused by idiopathic saccular dysfunction and/or utricular dysfunction.


Sephadex-based cell-affinity adsorbents: preparation and performance.
Sephadex was derivatized consecutively with Staphylococcus Protein A (SpA) and cell-specific antibodies, and the binding of cells to the resulting material was examined. For comparison, cell binding to commercially obtained SpA-Sepharose was determined. Sephadex G-10, carboxylated by reaction with glycine and activated subsequently with 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide/N-hydroxysuccinimide (NHS), was allowed to react with SpA. Coupling of SpA to NHS-activated glycine-Sephadex appeared to be complete (immobilization capacity, approximately 300 microg of protein/ml of packed gel) when incubation was carried out at pH 4.0, in buffer of low ionic strength. However, incubation at higher pH values (> or = 6.5) led to poor coupling yields. After incubation with rabbit anti-(human red cell) antiserum, and upon mixing with human red blood cells, SpA-glycine-Sephadex G-10 could bind up to 5 x 10(8) red cells/ml of gel. Cell binding increased when the amount of antiserum, added to SpA-glycine-Sephadex G-10 for preparing the affinity gel, was increased from 0.5 to 5 microl/ml of gel. Compared with this, SpA-Sepharose CL 4B had to be incubated with much larger amounts of antiserum (100-700 microl/ml of gel) in order to obtain cell-affinity adsorbent. One obvious advantage of the approach described here is that relatively small amounts of SpA and antisera are needed for preparing cell-affinity media.


Variations of the gallbladder in Sudanese subjects with literature review.
Advances in the use of laparoscopic surgery, especially in the biliary apparatus interference makes the need to revise the anatomical data of the gallbladder (GB) more important. Variations of the extra-hepatic biliary apparatus are characterized by large varieties of configurations. The aim of this article was to study the morphology of the GB in Sudanese subjects and review the common variations. Dissection of formalin-fixed cadavers' abdomens. GB is larger in Sudanese subjects than what is described in the standard text books. Congenital anomalies and anatomical variations of the extra-hepatic biliary tree, although not uncommon, can be of clinical importance. There are some differences in the only size of GB in Sudanese.


In vitro mitochondrial failure and oxidative stress mimic biochemical features of Alzheimer disease.
Primary cortical neurons exposed to the mitochondrial toxin NaN3 (0.1-3 mM) were submitted to oxidative stress with H2O2 (30-150 μM), to mimic conditions observed in neurodegenerative disorders. The effects of such treatment on a series of parameters useful in characterizing neuronal damage were investigated: (i) the basal release of glutamate, evaluated as (3)H-d-Aspartate efflux, was sharply, concentration-dependently, increased; (ii) the phosphorylation status of intracellular markers known to be involved in the neurodegenerative processes, in particular in Alzheimer disease: tau and GSK3β were increased, as well as the protein level of β-secretase (BACE1) and p35/25 evaluated by Western blotting, while (iii) the cell metabolic activity, measured with the MTT method, was reduced, in a concentration- and time-dependent manner. The latter effect, as well as tau hyperphosphorylation, was prevented both by a mixture of antioxidant drugs (100 μM ascorbic acid, 10 μM trolox, 100 μM glutathione) and by the anti-Alzheimer drug, memantine, 20 μM. Since it is well known that hippocampal cholinergic neurons are particularly affected in Alzheimer disease, the effects of NaN3 and H2O2 were also studied in electrically stimulated rat hippocampal slices, evaluating the (3)H-Choline efflux, as an index of acetylcholine release. The neurotoxic treatment depressed the neurosecretory function and the mixture of antioxidant drugs, as well as memantine, were able to restore it. The neuronal damage induced by the in vitro protocol adopted in the present work displays peculiarities of neurodegenerative disorders, e.g. Alzheimer disease, underlining the role of mitochondrial failure and oxidative stress, which appear to occur upstream the neurodegenerative process; such protocol could be utilized to test the efficacy of neuroprotective treatments.


Ethanol sensitivity in rats: effect of prenatal stress.
The present study examined whether sensitivity to ethanol could be altered by prenatal stress exposure. Pregnant female rats were handled during the third week of gestation and the offspring were tested for ethanol sensitivity as adults. Compared to control offspring, the following characteristic responses to acute ethanol were significantly attenuated in prenatally stress-exposed rats: the decreases in body temperature, motor coordination and startle amplitude, and the increases in circulating corticosterone and free fatty acids. Ethanol-induced impairment of swim performance, in contrast, was potentiated in these animals. Since no differences were found in blood or breath ethanol levels, the rate of ethanol metabolism was probably not affected by prenatal stress. Rather, the altered responses appear to result from long-term changes in central nervous system sensitivity to ethanol.


An integrated portable hand-held analyser for real-time isothermal nucleic acid amplification.
A compact hand-held heated fluorometric instrument for performing real-time isothermal nucleic acid amplification and detection is described. The optoelectronic instrument combines a Printed Circuit Board/Micro Electro Mechanical Systems (PCB/MEMS) reaction detection/chamber containing an integrated resistive heater with attached miniature LED light source and photo-detector and a disposable glass waveguide capillary to enable a mini-fluorometer. The fluorometer is fabricated and assembled in planar geometry, rolled into a tubular format and packaged with custom control electronics to form the hand-held reactor. Positive or negative results for each reaction are displayed to the user using an LED interface. Reaction data is stored in FLASH memory for retrieval via an in-built USB connection. Operating on one disposable 3 V lithium battery >12, 60 min reactions can be performed. Maximum dimensions of the system are 150 mm (h) x 48 mm (d) x 40 mm (w), the total instrument weight (with battery) is 140 g. The system produces comparable results to laboratory instrumentation when performing a real-time nucleic acid sequence-based amplification (NASBA) reaction, and also displayed comparable precision, accuracy and resolution to laboratory-based real-time nucleic acid amplification instrumentation. A good linear response (R2 = 0.948) to fluorescein gradients ranging from 0.5 to 10 microM was also obtained from the instrument indicating that it may be utilized for other fluorometric assays. This instrument enables an inexpensive, compact approach to in-field genetic screening, providing results comparable to laboratory equipment with rapid user feedback as to the status of the reaction.


Sustained release properties of the once daily theophylline capsule BY912 as compared with Theo-24 capsules.
In a multiple dose cross-over experiment in 12 healthy male adults the bioavailability and sustained release characteristics of new once daily BY912 400 mg theophylline capsules (= B, Byk Gulden Research Laboratories, FRG) were studied using Theo-24 capsules (= T, Searle & Co., USA) as reference. Both products were given once daily for a period of 7 days as an 800 mg theophylline dose at 8 am, half an hour after a standardized breakfast. Theophylline concentrations in plasma were measured on days 1, 6, and 7 using high-performance liquid chromatography. Significantly better sustained release characteristics, resulting in longer plateau time (t75%, 11.6 vs 9.2 h on day 6 and 13.1 vs 8.8 h on day 7) and smaller per cent peak-trough fluctuation in the steady state (per cent PTF, 80 vs 103 per cent on day 6 and 66 vs 100 per cent on day 7), were found for B in comparison with T. The extent of absorption on both days, however, was smaller for B compared with T (relative bioavailability 84 per cent and 81 per cent, respectively). In conclusion, the absorption of theophylline from B resulted in a more extended shape of the plateau phase, indicating better sustained release characteristics. The extent of absorption, however, over the dosing intervals was more complete with T.


Prognostic analysis for children with hepatoblastoma with lung metastasis: A single-center analysis of 98 cases.
To analyze the factors affecting the prognosis of hepatoblastoma (HB) with lung metastasis in children. The HB patients with lung metastases admitted to Beijing Tongren Hospital, Capital Medical University were collected. The clinical data, overall results, and prognostic factors were analyzed. Multivariate analysis was done by the Cox proportional hazards model for patients' prognosis. Finally, 98 HB patients (64 boys and 34 girls) with lung metastasis met the inclusion criteria, in which 64 patients had lung metastases at diagnosis (median age, 22.3 months) and 34 patients developed lung metastases while on treatment (median time, 6.5 months). The survival time and 5-year survival rate of patients with standard treatment were significantly longer than that of without standard treatment (P < .001). The survival time and 3-year survival rate had no difference between patients underwent lung metastasectomy and without lung metastasectomy (P = .099), between different diagnosis time of lung metastasis in HB patients (P = .37), between each histology type (P = .313), and different PRETEXT stage (P = .353). While the survival time and 3-year survival rate of patients with lung metastasis alone were significantly longer than that of patients with extrapulmonary involvement (P = .007). Multivariate Cox proportional hazards model revealed that the lung metastasis accompanied with extrapulmonary involvement was a risk factor affecting prognosis (HR = 0.460, 95% CI 0.239-0.888). For HB children with lung metastatic, extrapulmonary involvement might be a high-risk factor of prognosis and standardized treatment with lung metastasectomy might prolong the survival time of them.


Prospecting endophytic fungal assemblage of Digitalis lanata Ehrh. (foxglove) as a novel source of digoxin: a cardiac glycoside.
Endophytes, the chemical synthesizers inside plants, are the microorganisms having mutualistic relationship with the host plant. They can be used by plants for defense in addition to the production of a wide variety of beneficial bioactive secondary metabolites. There are reports that microbial endophytes mimic the bioactive compounds as produced by the plant itself thus making them a promising source of novel compounds. During the present study, endophytes were isolated from the symptomless leaves and stem of the angiosperm, Digitalis lanata (foxglove). Digitalis lanata belongs to the family Plantaginaceae and is an important medicinal plant known for the production of an important glycoside, digoxin having valuable medicinal importance. Glycosides from Digitalis have been reported to be cardiotonic and are widely used in the treatment of various heart conditions namely atrial fibrillation, atrial flutter, heart failure, etc. Endophytic fungi were isolated from Digitalis to screen them for such glycosides as have been found in the plant itself. A total of 35 fungal endophytes were isolated and screened for the production of secondary metabolites. After preliminary analysis by thin layer chromatography for the presence of bioactive compounds, crude extracts of five fungal cultures were selected for HPLC. HPLC chromatograms revealed the production of glycoside digoxin from the five selected endophytic cultures, thus providing a novel, alternative and eco-friendly source for the production of such a pharmaceutically important and valuable drug.


The Role of Physical Activity Enjoyment on the Acute Mood Experience of Exercise among Smokers with Elevated Depressive Symptoms.
Depressive symptoms are consistently shown to be related to poor smoking cessation outcomes. Aerobic exercise is a potential treatment augmentation that, given its antidepressant and mood enhancing effect, may bolster cessation outcomes for smokers with elevated depressive symptoms. Lower enjoyment of physical activity may inhibit the acute mood enhancing effects of aerobic exercise. The current study investigated the associations between depressive symptoms, physical activity enjoyment and the acute mood experience from exercise among low-active smokers with elevated depressive symptoms. Daily smokers with elevated depressive symptoms (N=159; Mage = 45.1, SD = 10.79; 69.8% female) were recruited for a randomized controlled exercise-based smoking cessation trial. Participants self-reported levels of depressive symptoms, physical activity enjoyment, and rated their mood experience (assessed as "mood" and "anxiety") before and after a standardized aerobic exercise test. Hierarchical regression analysis revealed that depressive symptom severity accounted for significant unique variance in physical activity enjoyment (R2 =.041, t = -2.61, p = .010), beyond the non-significant effects of gender and level of tobacco dependence. Additionally, physical activity enjoyment was a significant mediator of the association between depressive symptom severity and acute mood experience ("mood" and "anxiety") following the exercise test. Physical activity enjoyment may explain, at least in part, how depressive symptom severity is linked to the acute mood experience following a bout of activity. Interventions that target increasing physical activity enjoyment may ultimately assist in enhancing the mood experience from exercise, and therefore improve smoking cessation likelihood, especially for smokers with elevated depressive symptoms.


The Management of Vasovagal Syncope in a Patient with Brugada Syndrome.
Vasovagal syncope is the most common cause of the neurally mediated reflex syncopes. A higher susceptibility to vasovagal syncope has been reported in patients with Brugada syndrome (BrS) and may be caused by associated autonomic dysfunction. It is unclear what risk vasovagal syncope confers to patients with BrS. This article reviews the pathophysiology of vasovagal syncope and autonomic dysfunction in patients with BrS and its association with BrS, treatment options for patients with BrS with vasovagal syncope, specific therapies and those that may be harmful in patients with BrS, and potential therapies and monitoring for patients with BrS with vasovagal syncope.


Influence of nanomechanical crystal properties on the comminution process of particulate solids in spiral jet mills.
Elastic-plastic properties of single crystals are supposed to influence the size reduction process of bulk materials during jet milling. According to Pahl [M.H. Pahl, Zerkleinerungstechnik 2. Auflage. Fachbuchverlag, Leipzig (1993)] and H. Rumpf: [Prinzipien der Prallzerkleinerung und ihre Anwendung bei der Strahlmahlung. Chem. Ing. Tech., 3(1960) 129-135.] fracture toughness, maximum strain or work of fracture for example are strongly dependent on mechanical parameters like hardness (H) and young's modulus of elasticity (E). In addition the dwell time of particles in a spiral jet mill proved to correlate with the hardness of the feed material [F. Rief: Ph. D. Thesis, University of Würzburg (2001)]. Therefore 'near-surface' properties have a direct influence on the effectiveness of the comminution process. The mean particle diameter as well as the size distribution of the ground product may vary significantly with the nanomechanical response of the material. Thus accurate measurement of crystals' hardness and modulus is essential to determine the ideal operational micronisation conditions of the spiral jet mill. The recently developed nanoindentation technique is applied to examine subsurface properties of pharmaceutical bulk materials, namely calcite, sodium ascorbate, lactose and sodium chloride. Pressing a small sized tip into the material while continuously recording load and displacement, characteristic diagrams are derived. The mathematical evaluation of the force-displacement-data allows for calculation of the hardness and the elastic modulus of the investigated material at penetration depths between 50-300 nm. Grinding experiments performed with a modified spiral jet mill (Type Fryma JMRS 80) indicate the strong impact of the elastic-plastic properties of a given substance on its breaking behaviour. The fineness of milled products produced at constant grinding conditions but with different crystalline powders varies significantly as it is dependent on the nanohardness and the elasticity of the feed material. The analysis of this correlation gives new insights into the size reduction process.


The feasibility and acceptability of implementing video reflexive ethnography (VRE) as an improvement tool in acute maternity services.
Video-reflexive ethnography (VRE) has been argued to be an alternative approach to collaborative learning in healthcare teams, more able to capture the complexities of the healthcare environment than simulation. This study aims to explore the feasibility and acceptability of employing VRE as an improvement tool in acute maternity services. Focused ethnography and semi-structured interviews (n = 17) explored the feasibility of employing VRE from the perspective of the researcher-facilitator, and that of the healthcare staff participants. Reflexive thematic analysis was used to generate key themes. We identified four themes related to feasibility of employing VRE as an improvement approach: laying the groundwork; challenges of capturing in-situ video footage; effective facilitation of reflexive feedback; and, power to change. Of note was the central role of the facilitator in building and maintaining staff trust in the process, particularly in being able to guide collaborative, non-punitive discussion during reflexive feedback sessions. Interestingly, when considering implementation of change, structural hierarchies were evident with more senior staff better able to develop and effect ideas. Two themes related to acceptability of VRE among healthcare staff were identified: staff response to the role of VRE in improvement; and the power of a different perspective. Staff were overwhelmingly positive about their experience of VRE, particularly appreciating the time, space and autonomy it afforded them to navigate and articulate ideas for change and improvement. VRE is both feasible and acceptable as an improvement tool with acute, multi-disciplinary maternity staff teams. It is an important healthcare improvement tool that could prompt the development and maintenance of team resilience factors in the face of increasing stress and burn-out of healthcare staff in maternity services.


Some aspects of the synaptic circuitry underlying inhibition in the ventrobasal thalamus.
We describe here, and review, the ultrastructural features and synaptic relationships of flat-vesicle containing, presumptively inhibitory presynaptic elements in the glomerular and extraglomerular neuropils of the thalamic ventrobasal (VB) nucleus in monkey, cat and rat. This account is based on EM study of normal material, LM and EM immunocytochemistry for GABA, anterograde tracing with HRP and EM of physiologically characterized interneurons intracellularly injected with HRP. It emerges clearly from this study that attempts to categorize flat-vesicle containing terminals in thalamic tissue as either F-boutons (axon terminals with flattened synaptic vesicles and Gray type II synaptic specializations) or P-boutons (dendritic appendages of interneurons with flattened vesicles) by examining only single sections are likely to produce unreliable results. In many cases it is only by studying serial sections that such profiles can be unambiguously identified. Within glomeruli the P-boutons participate in triplet (triadic) synapses which are thought to mediate rapid feed forward inhibition of projection cells, and serial synaptic arrays involving other P-boutons. Since P-boutons from more than one interneuron are present in individual VB glomeruli, P-bouton to P-bouton synapses may mediate disinhibition of interneurons. We show that dendritic shafts of interneurons make and receive synaptic contacts and that in the monkey, at least, reciprocal synaptic contacts between shafts or between a shaft and a P-bouton are not uncommon. Finally, we confirm that in the rat VB there are insignificant numbers of P-boutons or cells with the morphological and transmitter characteristics of interneurons and we suggest that comparative electrophysiological studies of inhibitory events in rat VB versus those in cat or monkey VB during transmission of somatosensory information might help to clarify the roles of thalamic intrinsic neurons.


Comparative neurobehavioral study of a polybrominated biphenyl-exposed population in Michigan and a nonexposed group in Wisconsin.
An analysis of findings regarding the prevalence and time course of symptoms and the results of neurobehavioral testing among Michigan and Wisconsin dairy farmers, is reported. Reviewed are: (1) differences in the prevalence of neurological symptoms at the time of examination; (2) differences in the incidence and time course of symptoms for the period 1972--1976; (3) differences among populations and subgroups (sex and age) regarding performance test scores; (4) correlations between performance test scores and neurological symptoms; and (5) correlations between serum PBB levels as indicators of exposure and performance tests and neurological symptoms.


Association of urinary tract infection and reflux with uninhibited bladder contractions and voluntary sphincteric obstruction.
We studied 53 neurologically normal children with recurrent urinary tract infection who were found to have bladder-sphincter incoordination characterized by voluntary sphincteric constriction during involuntary uninhibited bladder contraction. Increased intravesical pressure was documented during these events and was associated with vesicoureteral reflux in nearly 50 per cent of the children and with abnormalities of the ureteral orifice in 30 per cent of those without reflux. We hypothesize that increased intravesical pressure causes urinary infection in these children and produces a spectrum of intravesical anatomic distortion that predisposes to vesicoureteral reflux. In a prospective uncontrolled study treatment of the uninhibited bladder contractions allowed 58 per cent of the patients to maintain sterile urine without subsequent antimicrobial therapy after cure of the initial infection.


[Bencyclane in stage II arterial occlusive disease. Results of a controlled study].
In a single-center, double-blind, randomized study, 19 patients with peripheral arterial occlusive disease stage II Fontaine were treated with bencyclan, and a further 19 patients with buflomedil for 10 weeks after a wash-out phase of 2 weeks. Both groups showed a significant increase in painfree and total walking distances. No significant difference was found between the two groups.


Retrograde transport of doxorubicin (adriamycin) in peripheral nerves of mice.
Doxorubicin (adriamycin) is a fluorescent compound which is widely used in the treatment of malignant tumors due to its capacity to bind and influence the DNA in the nucleus of cells. We have now observed that the compound after injection into a skeletal muscle of adult mice is transported to the corresponding nerve cell bodies, i.e. can be used as a retrograde tracer in neuroanatomical and neuropathological research. Six hours after injection into the tongue nerve cell nuclei were labeled in the hypoglossal nuclei of the brainstem. The fluorescent tracer had the same distribution as the chromatin. Glial nuclei in the vicinity of the hypoglossal neurons were also labeled presumably due to a transfer from the neurons to the glial cells during life or during the histochemical procedure. Since doxorubicin is also neurotoxic it might be a useful tool in neurobiological research, particularly if the labeled neurons later on will show toxic effects. In this way the compound could be used in models for experimental motor neuron disease and provide a means by which retrograde fluorescent tracing and a degeneration method can be combined for studies on various neuronal systems.


Barriers to helping patients quit smoking: Lack of knowledge about cessation methods, E-cigarettes, and why nurse practitioners and physician assistants can help.
Health care settings are ideal for addressing patients' smoking and quitting, but barriers may limit providers' assistance with cessation, including lack of knowledge about newer devices being used by some smokers to quit (e.g., e-cigarettes). Cessation practices among nurse practitioners (NPs) and physician assistants (PAs) are also unknown. Cross-sectional. Participants (N = 459) were 151 oncologists, 150 primary care physicians (PCPs), 98 nurse practitioners (NPs), and 60 physician assistants (PAs) recruited from a national online panel who completed an online survey. Four barriers were common across specialties: "patient doesn't want to quit, and it is their decision," "smoking is not reason for patient's visit; must treat the immediate problem first," "patient wants to quit on their own," and "lack of effective methods available." While a majority of oncologists (58%) were aware of free telephone counseling for cessation, only 29% of NPs were aware. Perceived knowledge of e-cigarettes was low. Greater comfort treating patients' smoking predicted greater frequency of engagement in 4 of 5 general cessation practices (βs = 0.15-0.26, all p ≤ .001). NPs and PAs more frequently asked patients about smoking and e-cigarette use compared to oncologists, but oncologists more frequently referred patients to effective quitting resources (e.g., quitlines). NPs and PAs may be uniquely positioned to provide cessation assistance, but providers need more education on currently available, effective cessation methods, and about e-cigarettes. Addressing patient resistance to offers of cessation services and improving clinical workflows to enhance cessation service provision should be investigated in future research.


The effects of blood pressure and antihypertensive drugs on heart failure: A Mendelian randomization study.
Heart failure (HF) is often triggered by hypertension and can benefit from antihypertensive treatment. We aimed to investigate whether pulse pressure (PP) could independently raise the risk of HF beyond systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as explore the potential mechanisms of antihypertensives in HF prevention. We generated genetic proxies for SBP, DBP, PP, and five drug classes based on a massive genome-wide association study. We applied two-sample Mendelian randomization (MR) using summary statistics derived from European individuals and conducted summary data-based MR (SMR) with gene expression data. In univariate analysis, PP showed an obvious association with HF risk (OR, 1.24 per 10 mm Hg increment; 95% CI, 1.16 to 1.32), which was largely attenuated in multivariable analysis when adjusted for SBP (0.89; 0.77 to 1.04). A significant decrease in HF risk was obtained with genetically proxied β-blockers (equivalent to a 10 mm Hg reduction in SBP, 0.71; 0.62 to 0.82) and calcium channel blockers (0.71; 0.65 to 0.78), but not with genetically proxied angiotensin-converting enzyme inhibitors (0.69; 0.40 to 1.19) and thiazide diuretics (0.80; 0.47 to 1.37). Additionally, the enrichment of expression for the KCNH2 gene, a target gene of β-blockers, in blood vessels and nerves was significantly associated with HF risk. Our findings suggest that PP may not be an independent risk factor for HF. β-blockers and calcium channel blockers have a protective effect against HF, which at least partly depends on their blood pressure-lowering effect.


Activity of traditional South African sedative and potentially CNS-acting plants in the GABA-benzodiazepine receptor assay.
Several plants are traditionally used to treat mental diseases in South Africa. Forty-six ethanol extracts from 35 species, both indigenous and exotic that are traditionally used predominantly as sedatives or to treat various CNS-related ailments were tested in the GABAA-benzodiazepine receptor-binding assay. In this assay, the binding of 3H-Ro 15-1788 (flumazenil) to the benzodiazepine site is measured. The GABAA-benzodiazepine receptor complex is involved in sedation, epilepsy and convulsions. Out of the 46 extracts tested, seven showed good activity and 10 showed moderate activity. The most active extracts were the ethanolic leaf extracts of Arctopus echinatus, Artemisa afra, four Helichrysum species and Mentha aquatica which all showed good dose-dependent activity.


Multislice CT coronary angiography: how to do it and what is the current clinical performance?
The introduction of multislice computed tomography (MSCT) has allowed non-invasive coronary angiography. Although widely applied, extensive information on technical details of the technique is lacking. This survey offers detailed information on patient preparation, data acquisition, reconstruction and interpretation. In addition, a summary of the available studies using MSCT for non-invasive angiography is provided. Based on pooled analysis of direct comparisons between MSCT and invasive angiography, the weighted mean sensitivity and specificity of current 16-slice MSCT for the detection of coronary artery disease are 88% and 96%, respectively. At present, the technique is particularly well suited for reliable exclusion of coronary artery disease. It is important to emphasise that MSCT only provides anatomical images, visualising the presence of atherosclerosis; information on the haemodynamic significance of these lesions (i.e. ischaemia) cannot be derived.


Regionlets for Generic Object Detection.
Generic object detection is confronted by dealing with different degrees of variations, caused by viewpoints or deformations in distinct object classes, with tractable computations. This demands for descriptive and flexible object representations which can be efficiently evaluated in many locations. We propose to model an object class with a cascaded boosting classifier which integrates various types of features from competing local regions, each of which may consist of a group of subregions, named as regionlets. A regionlet is a base feature extraction region defined proportionally to a detection window at an arbitrary resolution (i.e., size and aspect ratio). These regionlets are organized in small groups with stable relative positions to be descriptive to delineate fine-grained spatial layouts inside objects. Their features are aggregated into a one-dimensional feature within one group so as to be flexible to tolerate deformations. The most discriminative regionlets for each object class are selected through a boosting learning procedure. Our regionlet approach achieves very competitive performance on popular multi-class detection benchmark datasets with a single method, without any context. It achieves a detection mean average precision of 41.7 percent on the PASCAL VOC 2007 dataset, and 39.7 percent on the VOC 2010 for 20 object categories. We further develop support pixel integral images to efficiently augment regionlet features with the responses learned by deep convolutional neural networks. Our regionlet based method won second place in the ImageNet Large Scale Visual Object Recognition Challenge (ILSVRC 2013).


Generation of baculovirus expression vectors.
The baculovirus expression system has become an important tool for the expression of heterologous genes because it has several positives attributes. First, high quantities of protein are produced because the target genes are driven by strong viral promoters. Second, most eukaryotic posttranslational modifications are carried out in insect cells in an authentic manner. Thus, proteins expressed with the baculovirus expression system usually have the same activities as the authentic protein. Several approaches have been developed to obtain recombinant baculoviruses easily and nowadays many modified baculoviral DNAs and a huge variety of transfer plasmids are available. Here, we described the rapid generation of recombinant baculoviruses using parental viral DNA that incorporates a lethal deletion and can be selected against. This basic approach should be suitable for the majority of applications.


Father's Role in Preconception Health.
As part of the federal multi-agency conference on Paternal Involvement in Pregnancy Outcomes, the existing Fatherhood paradigm was expanded to include a new focus on Men's Preconception Health. This concept grew out of the women's preconception health movement and the maternal and child health (MCH) life course perspective, as well as pioneering research from the child development, public health data and family planning fields. It encourages a new examination of how men's preconception health impacts both reproductive outcomes and men's own subsequent health and development. This essay introduces the concept of men's preconception health and health care; examines its historical development; notes the challenges of its inclusion into fatherhood and reproductive health programs; and situates it within a longer men's reproductive health life course. We then briefly explore six ways men's preconception health and health care can have positive direct and indirect impacts-planned and wanted pregnancies (family planning); enhanced paternal biologic and genetic contributions; improved reproductive health biology for women; improved reproductive health practices and outcomes for women; improved capacity for parenthood and fatherhood (psychological development); and enhanced male health through access to primary health care. Research on men's preconception health and health care is very limited and siloed. We propose a research agenda to advance this topic in three broad domains: increasing the basic epidemiology and risk factor knowledge base; implementing and evaluating men's preconception health/fatherhood interventions (addressing clinical health care, psychological resiliency/maturation, and social determinants of health); and fostering more fatherhood health policy and advocacy research.


Pan-European survey of the topical ocular use of cyclosporine A.
To assess medical practices surrounding the use of topical ocular cyclosporine A across European Union nations. Key stakeholders (ophthalmologists, hospital pharmacists, regulatory health authorities) from European Union member states were interviewed by telephone using a semi-structured, open-ended questionnaire. Ophthalmologists responded to questions about practice patterns of cyclosporine A use (prescription frequency, indication, dosage), pharmacists about cyclosporine A formulations (composition, manufacturing process, quality control, distribution), and the regulatory authorities about market authorization and pharmacovigilance for various cyclosporine A products. Over the years, cyclosporine A use for ophthalmic indications has increased across all European Union nations. Prevalence of cyclosporine A use was heterogeneous, with Belgium, France, Germany, Italy, Portugal, Spain and the United Kingdom reporting the highest frequency. Compounded cyclosporine A formulations and other cyclosporine A products were prescribed through temporary authorization on a compassionate use or named-patient basis. Cyclosporine A was prescribed for dry eye disease, atopic and vernal keratoconjunctivitis, corneal graft rejection, and other autoimmune and inflammatory diseases. Concentrations of prescribed topical cyclosporine A ranged between 0.05-2% and formulations were instilled 1-6 times daily. Interviewed stakeholders expressed concern regarding, (1) paucity of product information, (2) lack of standardized manufacturing processes and quality control of cyclosporine A formulations, and (3) poor regulation and pharmacovigilance of ocular cyclosporine A-based products. Medical practice surrounding ocular cyclosporine A use in European Union nations differs based on variations in concentration, dosage, prescription indication, formulation, availability and distribution, manufacturing, quality, and regulatory monitoring.


Hobnail variant of papillary thyroid carcinoma with anaplastic dedifferentiation co-existent with tuberculosis lymphadenitis.
The current study aims to report a rare case of metastatic papillary thyroid carcinoma (PTC) of the cervical lymph nodes with hobnail variant and anaplastic de-differentiation. In addition to the primary disease, there was a second pathology which was caseating granulomatous lymph adenitis suggestive of tuberculosis. A 91-year-old female presented with a painful right sided neck swelling for two weeks, increased in size suddenly. On clinical examination, there was a well-defined firm painful right sided neck mass. On ultrasound examination, there was multiple well defined solid hypoechoic, hypervascular nodules. These resembled lymph nodes of variable size and shape, mostly in the right side. The patient underwent right lateral cervical lymph node dissection. After the operation, she was sent for radiotherapy. The hobnail variant of PTC is genetically identical to poorly differentiated thyroid carcinoma in that its mutations are in the p53 and TERT promoters are more common in this variant than in conventional PTCs. The proportion of hobnail features have no effect on the outcome. Additionally, 10% of tumor cells with hobnail features were previously linked to a more aggressive clinicopathological aspect. Although it is rare, metastatic PTC with hobnail variant could undergo anaplastic dedifferentiation.


The effects of mutations, deletions and insertions of single amino acids on the three-dimensional structure of globins.
Using the method of calculation of low energy packings of alpha-helices, we studied the effects of mutations, deletions and insertions of amino acids on the structure of sperm whale myoglobin. It was found that these events can cause complete breakdown of this structure.


Comparison of genetic diversity estimates within and among populations of maritime pine using chloroplast simple-sequence repeat and amplified fragment length polymorphism data.
We compared the genetic variation of Pinus pinaster populations using amplified fragment length polymorphism (AFLP) and chloroplast simple-sequence repeat (cpSSR) loci. Populations' levels of diversity within groups were found to be similar with AFLPs, but not with cpSSRs. The high interlocus variance associated with the AFLP loci could account for the lack of differences in the former. Although AFLPs revealed much lower genetic diversity than cpSSRs, the levels of among-population differentiation found with the two types of marker were similar, provided that loci showing fewer than four null-homozygotes, in any population, were pruned from the AFLP data. Moreover, the French and Portuguese populations were clearly differentiated from each other, with both markers. The Mantel test showed that the genetic distance matrix calculated using the AFLP data was correlated with the matrix derived from the cpSSRs. Because of the concordance found between markers we conclude that gene flow was indeed the predominant force shaping nuclear and chloroplastic genetic variation of the populations within regions, at the geographical scale studied.


Expression and detergent free purification and reconstitution of the plant plasma membrane Na+/H+ antiporter SOS1 overexpressed in Pichia pastoris.
The plant plasma membrane Na+/H+ antiporter SOS1 (Salt Overlay Sensitive 1) of Arabidopsis thaliana is the major transporter extruding Na+ out of cells in exchange for an intracellular H+. The sodium extrusion process maintains a low intracellular Na+ concentration and thereby facilitates salt tolerance. A. thaliana SOS1 consists of 1146 amino acids, with the first 450 in a N-terminal membrane transport domain and the balance forming a cytosolic regulatory domain. For studies on characterization of the protein, two different constructs of SOS1 comprising of the residues 28 to 460 and 28 to 990 were cloned and overexpressed in methylotropic yeast strain of Pichia pastoris with a C-terminal histidine tag using the expression vector pPICZA. Styrene malic acid copolymers (SMA) were used as a cost-effective alternative to detergent for solubilization and isolation of this membrane protein. Immobilized Ni2+-ion affinity chromatography was used to purify the expressed protein resulting in a yield of ~0.6-2 mg of SOS1 per liter of Pichia pastoris culture. The SMA purified protein containing amino acids 28 to 990 was directly reconstituted into liposomes for determination of Na+ transport activity and was functionally active. However, similar reconstitution with amino acids 28-460 did not yield a functional protein. Other results have shown that the truncated SOS1 protein at amino acid 481 is active, which infers the presence of an element between residues 461-481 which is necessary for SOS1 activity. This region contains several conserved segments that may be important in SOS1 structure and function.


Effect of cyclic nucleotides on the response of cells to infection by various herpesviruses.
The effect of varying the intracellular cyclic nucleotide concentration of mouse cells infected with HSV-1 or of duck embryo fibroblasts infected with Marek's disease virus has been studied. It has been shown in each case that agents that elevate the intracellular cAMP levels increase the yield of infectious virus or viral DNA, but inhibit cell division. cGMP enhances synthesis of viral DNA but allows continued synthesis of cell DNA.


Operational variables in high-performance gel filtration of DNA fragments and RNAs.
Double-stranded DNA fragments and ribosomal and transfer RNAs were measured by high-performance gel filtration on TSK-GEL G2000SW, G3000SW, G4000SW and G5000PW columns to investigate the separation range and resolution of these columns and the effects of eluent ionic strength and flow-rate on retention and resolution. These columns could separate double-stranded DNA fragments up to ca 1 X 10(6) and rRNAs up to ca 5 X 10(6) daltons in molecular weight. However, it was found that the selection of the column is very important to achieve optimum separation, depending on the molecular weight of the sample. Elution is delayed as the eluent ionic strength is increased. An eluent ionic strength of 0.3-0.5 seemed appropriate in most cases. Resolution is greatly increased as the flow-rate is decreased.


Seasonal onset of insulin dependent diabetes in relation to sex and age at onset.
All newly diagnosed insulin dependent diabetics presenting consecutively to the Diabetic Department of the Royal Infirmary from the City of Edinburgh or its environs, between the years 1964 and 1977, were analysed for sex (297 males, 205 females), age at diagnosis (range 10--75 years), month of diagnosis, duration of symptoms and month of symptomatic onset. Males aged 10--19 years showed a significant seasonal variation in diagnosis (p less than 0.025) with an increase in autumn and winter months which was not seen in females aged 10--19 years nor in patients of either sex aged more than 19 years at diagnosis. The duration of diabetic symptoms increased with increasing age at diagnosis in both males and females and was consistently greater in females than in males for each age group at diagnosis. When the month of symptomatic onset was considered in relation to sex and age at diagnosis, having excluded patients with duration of symptoms of more than three months, only males aged 10--19 years at diagnosis showed a significant seasonal variation in incidence (p less than 0.005).


Older cancer survivors' perspectives and use of telehealth in their cancer survivorship care in the United States: A ResearchMatch® sample.
COVID-19 has resulted in reliance on telecommunication technologies for the provision of supportive cancer care. However, research on the use of these resources among older adults, who are the majority of cancer survivors, is limited. The objective of this study was to gather information on older cancer survivors' perspectives and use of telehealth their cancer survivorship care in the United States. Potential participants were recruited through ResearchMatch® from December 2020-January 2021. Online semi-structured interviews were conducted. Descriptive statistics were used to analyze the participants' demographic and health characteristics. Content analysis were conducted by two independent coders for identification of common themes. Coding agreement was reached through consensus, and count comparisons of participant responses were made. The majority of respondents (n = 21; mean age = 73.5 ± 4.9) were female (57%), White (90%), and had a variety of cancer diagnoses. Participants reported using a variety of technology devices and telehealth products. Older cancer survivors (n = 10) endorsed telehealth video use for physical health concerns and basic check-ups, but some (n = 4) preferred in-person visits for major concerns and sensitive issues (e.g., mental health). Half of participants reported mobile health app use; however, ten participants did not use these apps as they felt the technology was not useful. Barriers to health technology use included missing face-to-face connections with providers, lack of familiarity with the technology, and perceived lack of utility and personalized telehealth platforms. Lastly, video-based conferencing and social media site use among seventeen participants was reported for social interaction during the COVID-19 pandemic. These findings suggest that older cancer survivors utilize online platforms for their general health; however, they prefer in-person visits for serious issues and value personalization with telehealth. Despite from a highly educated sample of ResearchMatch® participants, these results can be used to inform clinicians and researchers about the appropriateness and provision of telehealth-based supportive care among older cancer survivors.


Unwrapping Nephrogenic Rests and Nephroblastomatosis for Pediatric Surgeons: A Systematic Review Utilizing the PICO Model by the APSA Cancer Committee.
Nephrogenic rests (NR) may represent precursor lesions for Wilms tumor (WT), but their clinical course is not fully understood and no guidelines for treatment exist. This study sought to evaluate the outcomes of pediatric patients with NRs related to traditional chemotherapy and surgery. A PRISMA-P-compliant literature search was conducted in MEDLINE, Embase, CINAHL, Web of Science, COCHRANE, and SCOPUS from inception to June 2021. Clinical questions regarding the treatment of NRs, including chemotherapy and surgery, were developed in the population, intervention, comparison, and outcome format. Twenty-five studies including 1445 patients met inclusion criteria for evaluating chemotherapy compared to observation for NRs. Eighteen studies including 1392 patients met inclusion criteria for evaluating the role of surgery for NRs. Patients with isolated NRs who underwent observation progressed to WT 33% of the time; chemotherapy reduced the rate of WT to 3.9%. Observation of multiple NRs and diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) led to progression to WT 50% and 100% of the time, respectively. Chemotherapy reduced the rate of WT to 34% for multiple NRs and 46% for DHPLN. Surgery for isolated NRs reduced the risk of WT development from 23.7% in patients with incomplete excision to 3.3% with complete excision; however, 96% of patients with incompletely excised NRs had bilateral disease. Observation with close surveillance for isolated NRs is safe. Treatment with chemotherapy is recommended for patients with multiple NRs and DHPLN. Surgical management of NRs should focus on renal function preservation. Treatment study, Level III.


Ac-Ds solutions for rice insertion mutagenesis.
Rice is the model plant for monocotyledons. Since the completion of the high-quality sequence of its genome, the international community is deploying efforts to identify the function of the 30-40,000 nontransposable element genes of rice. These efforts comprise the creation of large collections of rice mutants accessible to the international scientific community. In addition to loss of function mutants, insertion mutagenesis using Agrobacterium-mediated transformation and engineered mobile elements allows the identification of genes through enhancer or gene trapping or activation tagging. The maize transposable element Ac-Ds is known to be active in rice since the early 1990s and it does not interfere with endogenous rice transposons. This is the guaranty that induced mutation obtained with the mobility of the Ds element will be stable when the source of Ac transposase is removed from the mutated genome. In this paper, we describe single- or double-component T-DNA constructs that have been used to introduce a functional Ac-Ds system in rice and allowed the generation and selection of different type of Ds insertion mutations in the rice genome.


Tracheal bronchus.
Tracheal bronchus is an aberrant bronchus that arises most often from the right tracheal wall above the carina and is the result of an additional tracheal outgrowth early in embryonic life. Its incidence ranges between 0.1 and 5%. This anomaly usually is diagnosed incidentally during bronchoscopy or bronchography performed for various respiratory problems. Occasionally, it represents the underlying etiology for chronic pulmonary disease such as emphysema, atelectasis, and persistent or recurrent pneumonia, especially if it involves the right upper lobe and reflects an abnormal pulmonary clearing mechanism. Tracheal bronchus may be associated with other bronchopulmonary anomalies, tracheal stenosis, or Down's syndrome. In the absence of clinical symptoms, a diagnosis of tracheal bronchus does not require any treatment. In patients with recurrent right upper lobe disease and a tracheal bronchus, therapy should include resection of the aberrant bronchus as well as the lobe it supplies.


Renal uptake of lutropin. Studies based on electron microscopic autoradiography and nephrectomy.
Nephrectomy of mature rats was found to result in a significant increase in the circulatory half-life of tritiated ovine lutropin. The interaction of the glycoprotein hormone with the kidneys was studied in a more direct fashion using electron microscopic autoradiography. Evidence is presented showing the transfer of the hormone from microvilli into tubular epithelia (probably via vesicular transport), where radioactivity then becomes associated with lysosomes. This provides direct support for related results based on subcellular fractionation in which renal lysosomal catabolism was suggested as being important in the degradation of tritiated lutropin (M. Ascoli, R. A. Liddle, and D. Puett, Molecular and Cellular Endocrinology 4, 297, 1976). These results add substantial weight to the growing evidence that the kidneys assume a major role in controlling the concentration of circulating macromolecules.


Misuse of Prescription Pain Relievers, Stimulants, Tranquilizers, and Sedatives Among U.S. Older Adults Aged ≥50 Years.
Misuse of prescription medications has led to higher mortality and morbidity in the U.S. This study investigates medical and nonmedical use of prescription medications (prescription pain relievers, stimulants, prescription tranquilizers, and sedatives) among adults aged ≥50 years. Data were from the 2015-2017 National Survey of Drug Use and Health. For each prescription medication, medical and nonmedical use were mutually exclusive (prescription pain relievers, stimulants, tranquilizers, and sedatives). Nonmedical use (misuse) was defined as the use of any prescription medications in greater amounts, frequency, or duration than prescribed or the use of medications without a prescription of the individual's own. Descriptive analysis was performed to assess prescription medication use and misuse among adults aged ≥50 years (pooled N=26,322). Correlates of misuse were assessed within multivariable logistic regression analyses at p<0.05. All analyses were conducted in 2019. In the past 12 months, 46.7% (51.7 million) of adults reported using any prescription medication, of which 7.7% (4.0 million) reported misuse. The proportion of past 12-month users reporting misuse was 5.4% for sedatives, 6.4% for prescription pain relievers, 6.5% for prescription tranquilizers, and 8.1% for stimulants. Overall, 16.2% (17.9 million) reported using 2 or more prescription medications within the past 12 months. Multiple prescription medication use was associated with female sex; White race; younger age; and use of nonprescription substances, including alcohol, tobacco, marijuana, and heroin. It is important to monitor medication misuse behaviors among older adults who may be living with several chronic conditions requiring pain management. The strong associations with serious psychological distress underscore the need for increased access to mental health services among this key population.


Balloon dilatation in children for oesophageal strictures other than those due to primary repair of oesophageal atresia, interposition or restrictive fundoplication.
Balloon dilatation of the oesophagus in children has been performed predominantly for treating strictures, which are the result of primary repair of oesophageal atresia, interposition surgery or restrictive Nissen's fundoplication. Reports of the use of this technique for alternative causes of stricture are few. To report our experience and success with balloon dilatation of strictures due to caustic ingestion, achalasia, oesophagitis, congenital stenosis, and epidermolysis bullosa (EB) and to make comparisons with our treatment of patients with primary repair of oesophageal atresia (OA), as well as with reports in the English language literature. Retrospective review of fluoroscopically guided balloon oesophageal dilatation procedures in 19 patients over a 5-year period, and comparison of those performed for OA repair complications with those due to other diseases. The average radiation dose, per procedure, was calculated by a medical physicist. Ten patients had strictures as a result of primary repair of OA. Three patients had stricture as a result of EB, two from achalasia, two from caustic injury, one due to an oesophageal web and one from reflux oesophagitis. Our results show that the technique can also be curative for the last group and that it may be used intermittently to alleviate symptoms in ongoing diseases. We have not experienced any complications and have also calculated that, even with prolonged use of multiple procedures, the radiation exposure is comparable to other radiological techniques. Patients with alternative causes for oesophageal stricture may be treated to resolution within 2 years using balloon dilatation. Ongoing diseases such as EB require ongoing dilatation, but balloon dilatation of strictures has been successful in alleviating swallowing difficulty. Patients with stricture from OA repair sometimes need ongoing dilatation. Radiation exposure for multiple procedures, over an extended period, is comparable to that from a single abdominal CT, and can be considered acceptable when repeat complex surgery is the alternative treatment option, or when ongoing incurable disease is the cause of the stricture.


1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer cells.
The effect of 1,25-dihydroxyvitamin D3 on lymphokine-activated killer (LAK) cells activity was studied. Treatment of LAK cells with 1,25-dihydroxyvitamin D3 for 24 h increased their cytotoxic activity without affecting cell proliferation. This effect was dose-dependent, detectable already at 10(-11) M attaining 44 +/- 7% increase at 10(-8) M. 1,25-dihydroxyvitamin D3 increased LAK cell content of the cytotoxic granule granzyme A by 21%. Secretion of granzyme A by LAK cells was triggered by 12-O-tetradecanoylphorbol 13-acetate and the calcium ionophore A23187. 1,25-dihydroxyvitamin D3 decreased the lag preceding secretion, increased the rate constant of exocytosis and the fraction of granzyme A cell content secreted. The potentiation of exocytosis was more pronounced at suboptimal calcium ionophore concentration suggesting that 1,25-dihydroxyvitamin D3 affects a calcium-dependent process. Since exocytosis of cytotoxic granules is a pivotal event in the killing of tumor cells by LAK cells, it is plausible that the enhancement of this process underlies the stimulation of LAK cell cytotoxic activity by 1,25-dihydroxyvitamin D3.


Survival and herpes virus production of normal and xeroderma pigmentosum fibroblasts after treatment with formaldehyde.
The survival of excision-deficient and of excision-proficient (variant) skin fibroblasts from xeroderma pigmentosum (XP) donors was about 5 times and twice, respectively, more sensitive to formaldehyde (FA) treatment than that of skin fibroblasts from healthy and XP heterozygote donors. The capacity of FA-treated host cells to further support Herpes virus (HSV) replication was also more sensitive to FA in XP12BE (group A) than in normal (KD) cells. An important recovery of this capacity occurred in both cell types when they were infected at increasing times (up to 36 h) after FA treatment. This contrasts with the decreasing capacity observed in XP12BE when similarly infected at increasing times after exposure to ultraviolet. In addition, the survival of FA-treated HSV was comparable in KD and XP12BE cells, whereas that of UV-irradiated HSV was much lower in XP12BE than in KD cells.


Morphological characteristics of the inner medullary zone in the kidneys of Brattleboro and Wistar rats during blockade of prostaglandin synthesis.
Morphological characteristics of the inner medullary zone in the kidneys in Brattleboro and Wistar rats were studied during blockade of prostaglandin synthesis. The absence of a diuretic effect of prostaglandins on the kidneys was accompanied by structural changes in the transepithelial and interstitial barriers for an osmotic flow of water.


Autoimmune mechanisms in pernicious anaemia & thyroid disease.
Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels.


Subgroup differences in psychosocial factors relating to coronary heart disease in the UK South Asian population.
To explore the differences in psychosocial risk factors related to coronary heart disease (CHD) between South Asian subgroups in the UK. South Asian people suffer significantly higher rates of CHD than other ethnic groups, but vulnerability varies between South Asian subgroups, in terms of both CHD rates and risk profiles. Psychosocial factors may contribute to the excess CHD propensity that is observed; however, subgroup heterogeneity in psychosocial disadvantage has not previously been systematically explored. With a cross-sectional design, 1065 healthy South Asian and 818 white men and women from West London, UK, completed psychosocial questionnaires. Psychosocial profiles were compared between South Asian religious groups and the white sample, using analyses of covariance and post hoc tests. Of the South Asian sample, 50.5% was Sikh, 28.0% was Hindu, and 15.8% was Muslim. Muslim participants were more socioeconomically deprived and experienced higher levels of chronic stress, including financial strain, low social cohesion, and racial discrimination, compared with other South Asian religious groups. In terms of health behaviors, Muslim men smoked more than Sikhs and Hindus, and Muslims also reported lower alcohol consumption and were less physically active than other groups. This study found that Muslims were exposed to more psychosocial and behavioral adversity than Sikhs and Hindus, and highlights the importance of investigating subgroup heterogeneity in South Asian CHD risk.


Reliability and validity of the Orthodontic Locus of Control Scale.
The Orthodontic Locus of Control (OLOC) Scale was developed to assess the ways in which persons perceive and evaluate the events that determine occlusal status and orthodontic treatment. The children's OLOC Scale is a 34-item self-administered inventory with a 6-point response format. The adult measure is a similar, 28-item version of the scale. A 6-item Occlusal Value Scale, was also developed for administration in conjunction with the OLOC Scale. These instruments were given to 51 children and their mothers who applied for treatment at the School of Dental Medicine's Orthodontic Clinic of the State University of New York at Buffalo. For validity studies, children and their mothers completed the Multidimensional Health Locus of Control (HLOC) Scale and the Orthodontic Opinion Poll (OOP) Subscales. The internal consistency estimates for reliability on both the child and parent versions of the OLOC Scales were in the moderate to high-moderate range. Moderate to high-moderate subscale correlations offer promise for the validity and usefulness of the Orthodontic Locus of Control Scale for future research on psychologic and social responses to malocclusion. The implications of the concept of "orthodontic locus of control" for orthodontists and parent-child treatment-related behaviors are discussed.


Expression and sub-cellular localization of the CCAAT/enhancer binding protein alpha in relation to postnatal development and malignancy of the prostate.
C/EBPalpha is a critical mediator of terminal differentiation and a tumor suppressor through its strong antiproliferative actions on cell cycle regulatory proteins. C/EBPalpha also appears to regulate androgen receptor (AR) AR signaling. There, is a paucity of information on the expression and sub-cellular localization of C/EBPalpha in normal mouse and human prostate and in prostate cancer. Immunohistochemistry of tissues including tissue arrays, quantitative polymerase chain reaction and mRNA expression database mining. In the mouse prostate epithelium, C/EBPalpha was present at 1 week postnatal localized in the cytosol, began to show nuclear localization at 8 weeks and continued to show prominent nuclear expression at 10 weeks and beyond; C/EBPalpha mRNA was expressed at all ages. In humans, C/EBPalpha showed prominent nuclear localization from peripubescence up to middle age but was sequestered in the cytosol in older individuals; the mRNA level for C/EBPalpha remained essentially unchanged. Most prostate adenocarcinomas expressed a range of levels of C/EBPalpha mRNA and protein that were relatively high in metastatic tumors in a manner that correlated with AR expression; however, most cells showed C/EBPalpha sequestered in the cytosol. Temporal changes in sub-cellular localization of C/EBPalpha are consistent with a role in prostate differentiation and as a prostate tumor suppressor; the cytoplasmic sequestration of C/EBPalpha, unique to older human prostates, is arguably a permissive condition for the greater frequency of proliferative disorders of the prostate. In malignant prostate C/EBPalpha may be available to regulate AR signaling through transient changes in its sub-cellular localization.


Contesting the natural in Japan: moral dilemmas and technologies of dying.
The paper opens with a discussion about the recognition of "whole-brain death" as the end of life in North America in order to perform solid organ transplants. This situation is contrasted with Japan, where, despite no financial or technological restrictions, brain death is not recognized, and transplants from brain-dead bodies cannot be performed. The Japanese cultural debate over the past twenty-five years about the "brain-death problem" is presented, followed by an analysis of Japanese attitudes towards technological intervention into what is taken to be the "natural" domain, together with a discussion of current Japanese attitudes towards death. This debate is interpreted as one aspect of a search for moral order in contemporary Japan, revealing ambivalence about self and other, Japan and the West, and tradition and modernity.


Daycare tonsillectomy: a safe outpatient procedure. Hospital Sultanah Bahiyah, Alor Setar Malaysia experience.
We present our experience with daycare tonsillectomy and evaluate patient satisfaction and the post operative complication rate. A prospective audit review of 38 patients from March 2009 till May 2010 was conducted in our ambulatory care center. There were 38 patients involved in this review. All patients were satisfied with our Ambulatory care services. No admission was reported after daycare tonsillectomy. Daycare tonsillectomy with or without adenoidectomy is safe. It can reduce the waiting time and also bed occupancy thus cost effective. Proper selection of patient is very important.


Worldwide trends in dairy production and consumption and calcium intake: is promoting consumption of dairy products a sustainable solution for inadequate calcium intake?
Adequate calcium intake is critical for good health. Inadequate calcium intake is a worldwide problem and is more serious in countries where consumption of dairy products is low. To analyze worldwide trends in production and consumption of dairy products and in calcium intake. Data were taken from Food and Agriculture Organization food balance sheets, from published studies, and from surveys of four countries with large populations and large dairy production (China, India, the United States, and Russia). Linear regression models were fitted to estimate average annual changes and to project future trends. Overall global dairy production and supply (total and per capita) have increased since 1980, especially in developing countries. There are large between-region and between-country differences in the levels of production, supply, and consumption and in the trends. In 1997 India surpassed the United States to become the largest dairy producer. Consumption of dairy products in China has more than tripled since 1982 and has increased sevenfold among urban residents. The increase has been more dramatic during recent years. In spite of increases in dairy production and consumption in China and India, calcium intake has decreased in these countries. The average daily per capita consumption of dairy products was more than 200 g in the United States in 1999-2004 but less than 27g in China in 2002; the average daily per capita intake of calcium was 962 mg in US men and 756 mg in US women in 1999-2004, but less than 400 mg in China in 2002. Global production and supply of dairy products have been increasing since 1980, which has an impact on the environment. Dairy consumption and calcium intake remain low in most countries examined as compared with recommended amounts of dairy products and calcium. Promotion of consumption of dairy products does not necessarily increase total calcium intake.


Colloidal and antibacterial properties of novel triple-headed, double-tailed amphiphiles: exploring structure-activity relationships and synergistic mixtures.
Two novel series of tris-cationic, tripled-headed, double-tailed amphiphiles were synthesized and the effects of tail length and head group composition on the critical aggregation concentration (CAC), thermodynamic parameters, and minimum inhibitory concentration (MIC) against six bacterial strains were investigated. Synergistic antibacterial combinations of these amphiphiles were also identified. Amphiphiles in this study are composed of a benzene core with three benzylic ammonium bromide groups, two of which have alkyl chains, each 8-16 carbons in length. The third head group is a trimethylammonium or pyridinium. Log of critical aggregation concentration (log[CAC]) and heat of aggregation (ΔHagg) were both inversely proportional to the length of the linear hydrocarbon chains. Antibacterial activity increases with tail length until an optimal tail length of 12 carbons per chain, above which, activity decreased. The derivatives with two 12 carbon chains had the best antibacterial activity, killing all tested strains at concentrations of 1-2μM for Gram-positive and 4-16μM for Gram-negative bacteria. The identity of the third head group (trimethylammonium or pyridinium) had minimal effect on colloidal and antibacterial activity. The antibacterial activity of several binary combinations of amphiphiles from this study was higher than activity of individual amphiphiles, indicating that these combinations are synergistic. These amphiphiles show promise as novel antibacterial agents that could be used in a variety of applications.


Regioselective Magnesiation and Zincation Reactions of Aromatics and Heterocycles Triggered by Lewis Acids.
Mixed TMP-bases (TMP=2,2,6,6-tetramethylpiperidyl), such as TMPMgCl ⋅ LiCl, TMP2 Mg ⋅ 2LiCl, TMPZnCl ⋅ LiCl and TMP2 Zn ⋅ 2LiCl, are outstanding reagents for the metalation of functionalized aromatics and heterocycles. In the presence of Lewis acids, such as BF3 ⋅ OEt2 or MgCl2 , the metalation scope of such bases was dramatically increased, and regioselectivity switches were achieved in the presence or absence of these Lewis acids. Furthermore, highly reactive lithium bases, such as TMPLi or Cy2 NLi, are also compatible with various Lewis acids, such as MgCl2 ⋅ 2LiCl, ZnCl2 ⋅ 2LiCl or CuCN ⋅ 2LiCl. Performing such metalations in continuous flow using commercial setups permitted practical and convenient reaction conditions.


Rising incidence of Enterococcus species in microbiological specimens from orthopedic patients correlates to increased use of cefuroxime: a study concentrating on tissue samples.
Enterococci are emerging causes of severe infections, including wound and bone infections in orthopedic patients. The main purpose of this study was to determine whether there was a correlation between the incidence of enterococci in tissue samples (biopsies) from orthopedic patients and consumption of cefuroxime in the orthopedic department. Data were obtained from the department of clinical microbiology and the hospital pharmacy. The consumption of cefuroxime successively increased from 40 defined daily doses (DDD)/10(3) bed days in 2002 to 212 DDD/10(3) bed days in 2009. The incidence of patients with enterococci in tissue samples increased steadily from 1.03/10(3) bed days in 2002 to 5.90/10(3) bed days in 2009. Regression analysis revealed a significant correlation between the consumption of cefuroxime and the incidence of enterococci. Continuous surveillance of species distribution, resistance rates, and antibiotic consumption is of utmost importance for optimal antibiotic strategy in orthopedic patients.


Changes in cellular and biochemical profiles of induced sputum after allergen-induced asthmatic response: method for studying occupational allergic airway inflammation.
The purpose of the study was to analyze morphological and biochemical changes in induced sputum after the provocation with occupational allergens (mixture of flours and grains) in subjects with diagnosed occupational asthma. Subjects with occupational asthma and healthy volunteers had physical examination, skin prick tests with common and occupational allergens, and spirometry. Specific IgE against common and occupational allergens was also measured. Bronchial inflammation was characterized by the percentage of cells, levels of eosinophil cationic protein (ECP), and changes in mucosal permeability index. There was a significant increase in the proportion of eosinophils, basophils, lymphocytes, and in the ECP level in induced sputum of occupational allergics after the specific provocation. Sputum induction is a reliable method for measuring allergen-induced airway inflammation.


Spintronics: spin accumulation in mesoscopic systems.
In spintronics, in which use is made of the spin degree of freedom of the electron, issues concerning electrical spin injection and detection of electron spin diffusion are fundamentally important. Jedema et al. describe a magneto-resistance study in which they claim to have observed spin accumulation in a mesoscopic copper wire, but their one-dimensional model ignores two-dimensional spin-diffusion effects, which casts doubt on their analysis. A two-dimensional vector formalism of spin transport is called for to model spin-injection experiments, and the identification of spurious background resistance effects is crucial.


Genetic etiology of the common liability to drug dependence: evidence of common and specific mechanisms for DSM-IV dependence symptoms.
We investigated the etiological nature of comorbid alcohol, tobacco, and cannabis DSM-IV dependence symptoms in late adolescence and young adulthood while accounting for gender differences in the magnitude of genetic and environmental influences. Univariate and multivariate twin modeling was used to determine the heritability of each substance and the etiology of multiple drug problems in a sample of 2484 registrants of the Center for Antisocial Drug Dependence who provided data at the second wave of an ongoing longitudinal study. We report on mean and prevalence levels of whole-life DSM-IV dependence symptoms that were assessed with the Composite International Diagnostic Interview-Substance Abuse Module. Biometrical analyses were limited to age-adjusted DSM-IV dependence symptom counts from a subset of twins that reported using alcohol, tobacco, or cannabis in their lifetime. Male and female alcohol, tobacco, and cannabis DSM-IV symptoms are indicators of a heritable unidimensional latent continuous trait. Additive genetic factors explain more than 60% of the common liability to drug dependence. A larger proportion of the variation in each substance is attributable to substance-specific genetic and environmental factors. These data suggest that both common and substance-specific genetic and environmental factors contribute to individual differences in the levels of DSM-IV alcohol, tobacco, and cannabis dependence symptoms.


Osteoid osteoma of the neck of the talus: percutaneous, computed tomography-guided technique for complete excision.
CT-guided core drill excision of talar neck osteoid osteomas, in addition to other locations, appears to be a promising alternative to standard surgical treatment. As in this report, the technique is minimally invasive, which allows for complete, accurate excision and early return to activity.


Placenta previa-accreta: risk factors and complications.
The purpose of this study was to identify risk factors and complications of placenta previa-accreta (PA). Patients with placenta previa (n = 347) delivered over 20 years were reviewed, divided into PA (cases, n = 22) and no accreta (controls, n = 325), and compared. Cases were older with a higher incidence of smoking and previous cesarean delivery (CS). Grandmultiparity, recurrent abortions, anterior/central placentae, and low socioeconomic status were similar. PA incidence increased with the number of previous CS: 1.9%, 15.6%, 23.5%, 29.4%, 33.3%, and 50.0% after 0, 1, 2, 3, 4, and 5 previous CS, respectively. Hypertensive disorders (odds ratio [OR] 13.9, 95%CI 2.1-91.2], P = .006), smoking (OR 3.4, 95%CI 1.1-10.2, P = .031) and previous CS (OR 7.9, 95%CI 1.7-37.4, P = .009) were selected by the stepwise logistic regression analysis as predictors of PA. Cases had a longer hospital stay, a higher estimated blood loss, and need for transfusion. Cesarean hysterectomy and hypogastric artery ligation were only performed in PA cases. The 2 groups had a similar delivery gestational age and neonatal outcome. Hypertensive disorders, smoking, and previous cesarean are risk factors for accreta in placenta previa patients. Placenta previa-accreta is associated with higher maternal morbidity, but similar neonatal outcome compared with patients with an isolated placenta previa.


Photodegradation of haloacetic acids in water.
The global distribution and high stability of some haloacetic acids (HAAs) has prompted concern that they will tend to accumulate in surface waters and pose threats to humans and the ecosystem. It is important to study the degradation pathways of HAAs in aqueous systems to understand their ecotoxicological effects. Previous studies involving thermal degradation reactions show relatively long lifetimes for HAAs in the natural environment. Photolysis and photocatalytic dissociation are potentially efficient routes for the degradation of HAAs such as trichloroacetic acid to hydrochloric acid, carbon dioxide and chloroform, although such processes are poorly understood in surface waters. In our present study, we have used light to degrade the HAAs in the presence of titanium dioxide suspensions. All chloro and bromo HAAs degrade in photocatalysis experiments and the rate of degradation is directly proportional to the number of halogen atoms in the acid molecule. The half-lives of the HAAs from the photodegradation at 15 degrees C in the presence of suspended titanium dioxide photocatalyst are 8, 14, 83 days for the tri-, di- and mono-bromoacetic acids. Tri-, di- and mono-chloroacectic acids have half-lives of 6, 10 and 42 days respectively. The mixed bromochloro and chlorodifluoroacetic acids degrade with half-lives of 18 and 42 days respectively. Our results therefore suggest that the photocatalytic process can provide an additional degradation pathway for the HAAs in natural waters.


Structural studies on glycolipid of shellfish. II. Occurrence of 3-O-methylgalactosamine in oyster glycolipid.
3-O-Methyl hexosamine was found for the first time and characterized as one of the sugar components of oyster glycolipid. The alditol acetate of this sugar was identified as 3-O-methyl-N-acetylgalactosaminitol acetate by comparing its retention time on gas chromatography and mass spectrum with those of the authentic sample synthesized in this laboratory. The new sugar, 3-O-methylgalactosamine, occupied the non-reducing terminal position of the carbohydrate moiety of the lipid and was linked to the penultimate hexose by a (1 leads to 3) bond.


Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.
Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.


The kinetics of pancreatic ribonuclease reaction with alkaline and acidic forms of poly A.
The RNase hydrolysis of random-coil (alkaline form) poly A follows biphasic kinetics at low salt concentrations. However, its resistance to RNase increases with the ionic strength. Helical (acidic form) poly A is alos susceptible to RNase but its hydrolysis follows first-order kinetics, and its resistance increases as the pH is lowered. These conformation-dependent kinetics of poly A hydrolysis are similar to those obtained in the hydrolysis of cellular RNA and reovirus double-stranded RNA.


A systematic review on clinical features and management of true giant splenic artery aneurysms.
True giant splenic artery aneurysms (GSAAs) >5 cm are rare and present unique therapeutic challenges. The aim of this study was to evaluate the anatomic and clinical characteristics of these lesions and the current surgical and endovascular techniques available for their treatment. A systematic review of the literature from 2004 to 2018 and the personal experience of the authors with management of GSAAs are presented. A total of 92 GSAA cases were reviewed. Analyses were performed on anatomic and clinical features and management modalities and outcomes of GSAA, including reintervention, morbidity, and mortality. GSAA presented at a mean age of 56.1 ± 17.3 years, with no sex predilection; 73% were symptomatic at presentation. Abdominal pain was the presenting symptom in >50% of cases; 34% percent were ruptured, with an overall mortality rate of 12.5%. This group often presented with gastrointestinal bleeding or hemodynamic collapse. The aneurysms were almost evenly distributed across the splenic artery and were not uncommonly associated with arteriovenous fistula formation (8.7%). There were 88 patients who had surgical (53.4%), endovascular (44.3%), or combination (2.3%) therapy. The most commonly performed procedure was aneurysmectomy and splenectomy with or without additional resection. Overall, surgical treatment had a lower morbidity (P = .041) than endovascular therapy and comparable reintervention and mortality rates. GSAAs are uncommon vascular lesions, with distinct clinical features and aneurysm characteristics. Considering their high risk of rupture, timely diagnosis and management are essential to attain a satisfactory outcome. Surgery remains the standard treatment of these lesions. Endovascular intervention is a viable alternative in high-risk patients, particularly those with lesions <10 cm or with anomalous origin.


Pilot survey of aflatoxin-albumin adducts in sera from Egypt.
Aflatoxins are potent liver carcinogens that frequently contaminate cereals in developing countries. Aflatoxin exposure has been predicted in Egypt but, to date, no studies have measured the level of aflatoxin-albumin (AF-alb) adducts as a validated biomarker to assess exposure. In this pilot survey, a limited number of sera samples, available from a hepatocellular carcinoma (HCC) case-control study in Egypt, were analysed. AF-alb was detected in 24/24 samples from HCC-negative individuals (geometric mean 9.0 pg mg(-1); range 3.5-25.8pg mg(-1)), while 7/22 samples from HCC-positive cases had detectable AF-alb (geometric mean 2.6 pg mg(-1); range: non-detectable-32.8 pg mg(-1)). These AF-alb data do not represent a case-control comparison due to inherent difficulties in comparing markers of dietary intake between controls and patients with disease. Although these data are limited, the potential health consequences of aflatoxin exposure in this region merit further investigation.


Indicators, trends, and recommendations for living a longer, healthier life.
Radiology faculty members serve as role models to residents and medical students, potentially influencing the choices trainees make regarding their health. Resident work hours, program flexibility in work hours, food served at department functions, wellness programs offered by programs or the institutions in which they are housed, and subtle cues that reflect faculty values regarding personal and community health are examples of factors that potentially influence the choices made by trainees. There are many unanswered questions regarding the adequacy of training programs in promoting good health among their trainees. One purpose of this review is to lay the groundwork for research in how radiology training programs influence trainees' compliance with health recommendations. It focuses on physical activity, overweight and obesity, and related health concerns. It emphasizes the discouraging fact that the majority of American adults do not follow recommended guidelines for physical activity and diet, worker stress among American adults is high, 1 in 4 American adults have high blood pressure, and more than 20% have high levels of total cholesterol.


Neuroimaging for patient selection for medial temporal lobe epilepsy surgery: Part 2 functional neuroimaging.
We evaluate and discuss the various functional imaging techniques that are currently in use to assess the eligibility of a refractory temporal lobe epilepsy (TLE) patient for treatment with medial temporal lobe surgery. The assessment of eligibility for treatment is challenging and relies heavily on functional imaging modalities that provide physiological information, in addition to structural data acquired by different imaging techniques. This review is the final segment of a two part study, the first of which focused on the structural and anatomical imaging modalities that are in use for the surgical treatment of TLE. The authors performed a comprehensive query of PubMed, Embase and Medline databases in search of all relevant English language studies that were published between 1990 and 2013. Overall, 56 papers were reviewed (50% of them covering primarily functional neuroimaging), including a total of 1517 patients. The extracted data included the general study identification, demographics, population, study design, neuroimaging methods, reference standard imaging method used (gold standard), outcomes, and conclusions. As the majority of the studies investigated functional MRI, single photon emission computed tomography and positron emission tomography, the authors focus the review on these specific modalities.


Patients' and informal caregivers' perspectives on self-management interventions for type 2 diabetes mellitus outcomes: a mixed-methods overview of 14 years of reviews.
Self-management interventions (SMIs) are core components of high-quality care in type 2 diabetes mellitus (T2DM). We aimed to identify and summarise the scientific evidence exploring the perspectives of patients with T2DM and their informal caregivers on outcomes of SMIs, and the key themes to enhance T2DM patient-centred care. We conducted a mixed-methods overview of reviews. We searched MEDLINE, CINAHL and PsycINFO, up to June 2021 for systematic reviews (SRs) exploring the perspectives of adults with T2DM and their informal caregivers, regarding self-management. Two reviewers conducted independently study selection, data extraction and quality assessment. We estimated the degree of overlap across SRs. We performed a qualitative analysis using a thematic synthesis approach. We identified 54 SRs, corresponding to 939 studies, with a slight overlap. Most SRs (47/54, 87%) were considered high quality. We developed summaries for 22 outcomes and identified six overarching themes: (1) diabetic identity; (2) accessing healthcare; (3) experience of care; (4) engagement with self-management; (5) outcomes awareness; and (6) challenges adhering to self-management. We found important variability in how patients with T2DM and their informal caregivers value critical outcomes influenced by the disease progression and several contextual factors. Our findings represent what matters most to patients with T2DM and their informal caregivers regarding outcomes of SMIs. Our results can facilitate the development and evaluation of SMIs, and guide decision-making in diabetes care, including the formulation of decisions and recommendations.


Effects of gender and dementia severity on Alzheimer's disease caregivers' sleep and biomarkers of coagulation and inflammation.
Being a caregiver for a spouse with Alzheimer's disease is associated with increased risk for cardiovascular illness, particularly for males. This study examined the effects of caregiver gender and severity of the spouse's dementia on sleep, coagulation, and inflammation in the caregiver. Eighty-one male and female spousal caregivers and 41 non-caregivers participated (mean age of all participants 70.2 years). Full-night polysomnography (PSG) was recorded in each participants home. Severity of the Alzheimer's disease patient's dementia was determined by the Clinical Dementia Rating (CDR) scale. The Role Overload scale was completed as an assessment of caregiving stress. Blood was drawn to assess circulating levels of D-dimer and Interleukin-6 (IL-6). Male caregivers who were caring for a spouse with moderate to severe dementia spent significantly more time awake after sleep onset than female caregivers caring for spouses with moderate to severe dementia (p=.011), who spent a similar amount of time awake after sleep onset to caregivers of low dementia spouses and to non-caregivers. Similarly, male caregivers caring for spouses with worse dementia had significantly higher circulating levels of D-dimer (p=.034) than females caring for spouses with worse dementia. In multiple regression analysis (adjusted R(2)=.270, p<.001), elevated D-dimer levels were predicted by a combination of the CDR rating of the patient (p=.047) as well as greater time awake after sleep onset (p=.046). The findings suggest that males caring for spouses with more severe dementia experience more disturbed sleep and have greater coagulation, the latter being associated with the disturbed sleep. These findings may provide insight into why male caregivers of spouses with Alzheimer's disease are at increased risk for illness, particularly cardiovascular disease.