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While poverty is an established barrier to achieving success at each step of the HIV care continuum, less is known about specific aspects of poverty and how they overlap with behavior in exceptionally low-income individuals who live in well-resourced areas. We considered unsuppressed viral load over three years among women living with HIV in San Francisco who used homeless shelters, low-income hotels and free meal programs. One-hundred twenty study participants were followed; 60% had ≥1 unsuppressed viral load and 19% were unsuppressed at every visit. Across six-month intervals, the odds of unsuppressed viral load were 11% higher for every 10 nights spent sleeping on the street (Adjusted Odds Ratio [AOR] =1.11, 95% CI:1.02-1.20); 16% higher for every 10 nights spent sleeping in a shelter (AOR/10 nights= 1.16, 95% CI: 1.06-1.27); 4% higher for every 10 nights spent sleeping in a single-room occupancy hotel (AOR/10 nights= 1.04, 95% CI: 1.02-1.07); and almost four-fold higher among women who experienced any recent incarceration (AOR=3.56, 95% CI: 1.84-6.86). Violence and recent use of outpatient health care did not significantly predict viral suppression in adjusted analysis. While strategies to promote retention in care are important for vulnerable persons living with HIV, they are insufficient to ensure sustained viral suppression in low-income women experiencing homelessness and incarceration. Results presented here in combination with prior research linking incarceration to homelessness among women indicate that tailored interventions, which not only consider but prioritize affordable housing, are critical to achieving sustained viral suppression in low-income women living with HIV.

BACKGROUND: Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies. METHODS: To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes using 2 cohorts of patients with S. aureus bacteremia (n = 32 and n = 124). RESULTS: We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia. Prognostic modeling identified interleukin (IL)-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers classifying fatal outcome with 89% sensitivity and 77% specificity (P < .0001). Baseline IL-17A levels were elevated in patients with persistent bacteremia (P < .0001), endovascular (P = .026) and metastatic tissue infections (P = .012). CONCLUSIONS: These results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials.

Circadian rhythms drive the timing of daily physiological functions, including food intake. These cellular rhythms depend on the intricate regulation of core clock genes, such as BMAL1. Disruptions of the molecular clock in rodents have been shown to induce obesity and features of the metabolic syndrome, as well as altering diurnal food intake patterns. In vitro studies using palmitate, a saturated fatty acid comprising a large portion of high-fat diets, demonstrate alterations in hypothalamic BMAL1 and feeding-related neuropeptide expression. We hypothesized that the high-fat, high-sugar (Western) diet alters circadian food intake rhythms by altering hypothalamic feeding-related neuropeptide expression in a BMAL1-dependent manner. C57BL/6-J mice were fed either rodent chow (RC; control) or Western diet (WD) for 16 weeks. Male and female WD mice gained more weight compared to controls, and consumed a larger proportion of their food during the inactive (light) period. Hypothalamic mRNA expression patterns of neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC) were markedly altered by WD feeding. Compared to RC controls, WD mice showed a blunted mRNA expression of AgRP and NPY, accompanied by an altered hypothalamic expression of the clock genes BMAL1 and Per2. To identify the cellular mechanism by which the WD affects the central control of food intake, hypothalamic cell lines were derived from adult BMAL1-wildtype (WT) and knockout (KO) C57BL/6-J mice. Hypothalamic primary cultures were immortalized with SV40 T-antigen and characterized to demonstrate a robust rhythmic cycling of clock gene expression, in addition to the expression of several neuropeptides. Importantly, BMAL1-WT neurons exhibited a 24-hour period in Per2 clock gene mRNA expression, while the BMAL1-KO cell line lacked rhythmic expression of Per2, confirming the cell line as a hypothalamic model of circadian disruption. Additionally, the expression patterns of NPY, AgRP, and POMC were altered with BMAL1 knockout. Treatment with palmitate increased BMAL1, Per2, and POMC expression at 9 or 21 hours, corresponding to the peak and trough of clock and neuropeptide mRNA expression. Taken together, these results suggest a role for the circadian clock in regulating hypothalamic neuropeptide expression and, thereby, central control of food intake. Sources of research support: MNC has received graduate awards from the Banting and Best Diabetes Centre and the Ontario Graduate Scholarship; studies were supported by CIHR and NSERC operating grants. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Background Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with antibiotics to prevent relapse due to the ability of SA to establish reservoirs of infection in sites such as heart and bone. These metastatic sites of infection cannot be serially sampled to monitor the clearance of SA infection. This study aimed to establish a link between persistence of circulating SA deoxyribonucleic acid (SA-DNA) and tissue reservoirs in patients with SA bacteremia. Methods A highly sensitive quantitative polymerase chain reaction was used to measure whole blood SA-DNA and plasma-derived SA cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 73 patients with confirmed SA bacteremia and correlated with clinical features. Results Blood SA-DNA was detected for longer than the duration of positive blood cultures. Longer duration of circulating bacterial DNA was observed in complicated SA bacteremia infections, such as endocarditis and osteoarticular infections, compared with uncomplicated bloodstream infections. In contrast, traditional blood cultures demonstrated similar time to clearance regardless of foci of infection. Plasma-derived SA-cfDNA showed concordance with blood SA-DNA levels. Baseline levels of SA-DNA were higher in patients presenting with greater clinical severity and complicated bacteremia. Conclusions Prolonged levels of circulating SA-DNA in patients with complicated tissue reservoirs after clearance of blood cultures observed in this single-center study should be validated in additional cohorts to assess the potential utility for monitoring clearance of infection in patients with SA bacteremia.

Paraneoplastic syndromes are often a diagnostic challenge to doctors and may have a heterogeneous presentation, including humoral hypercalcemia of malignancy (HHM), most commonly caused by squamous cell cancer and renal, ovarian, endometrial, and breast cancer. Chronic inflammatory demyelinating polyneuropathy (CIDP) has been described in patients affected by several types of cancer, especially hematologic malignancies, and a possible paraneoplastic pathogenesis of this neurological disease has been suggested. This report describes a 56-year-old man with a history of CIDP diagnosed 3 months earlier and persistently elevated aminotransferases for 18 months who was admitted to our internal medicine unit with abdominal pain, fatigue, and severe hypercalcemia with low serum intact parathyroid hormone. Parathyroid hormone-related protein (PTH-rP) was markedly high. Liver imaging showed a large hepatic mass in the right lobe, and percutaneous ultrasound-guided biopsy revealed histopathological findings consistent with a combined hepatocholangiocarcinoma (CHCC). We supposed that both HHM and CIDP could represent a paraneoplastic manifestation of CHCC.

Background Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with antibiotics to prevent relapse due to the ability of SA to establish reservoirs of infection in sites such as heart and bone. These metastatic sites of infection cannot be serially sampled to monitor the clearance of SA infection. This study aimed to establish a link between persistence of circulating SA deoxyribonucleic acid (SA-DNA) and tissue reservoirs in patients with SA bacteremia. Methods A highly sensitive quantitative polymerase chain reaction was used to measure whole blood SA-DNA and plasma-derived SA cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 73 patients with confirmed SA bacteremia and correlated with clinical features. Results Blood SA-DNA was detected for longer than the duration of positive blood cultures. Longer duration of circulating bacterial DNA was observed in complicated SA bacteremia infections, such as endocarditis and osteoarticular infections, compared with uncomplicated bloodstream infections. In contrast, traditional blood cultures demonstrated similar time to clearance regardless of foci of infection. Plasma-derived SA-cfDNA showed concordance with blood SA-DNA levels. Baseline levels of SA-DNA were higher in patients presenting with greater clinical severity and complicated bacteremia. Conclusions Prolonged levels of circulating SA-DNA in patients with complicated tissue reservoirs after clearance of blood cultures observed in this single-center study should be validated in additional cohorts to assess the potential utility for monitoring clearance of infection in patients with SA bacteremia.

Background People living with HIV (PLWH) who experience homelessness and unstable housing (HUH) often have fragmented health care. Research that incorporates granular assessments of housing status and primary care visit adherence to understand patterns of acute care utilization can help pinpoint areas for intervention. Methods We collected self-reported living situation, categorized as stable (rent/own, hotel/single room occupancy), unstable (treatment/transitional program, staying with friends), or homeless (homeless shelter, outdoors/in vehicle) at an urban safety-net HIV clinic between February and August 2017 and abstracted demographic and clinical information from the medical record. Regression models evaluated the association of housing status on the frequency of acute care visits—urgent care (UC) visits, emergency department (ED) visits, and hospitalizations—and whether suboptimal primary care visit adherence ( Results Among 1198 patients, 25% experienced HUH. In adjusted models, unstable housing resulted in a statistically significant increase in the incidence rate ratio for UC visits (incidence rate ratio [IRR], 1.35; 95% confidence interval [CI], 1.10 to 1.66; P < .001), ED visits (IRR, 2.12; 95% CI, 1.44 to 3.13; P < .001), and hospitalizations (IRR, 1.75; 95% CI, 1.10 to 2.77; P = 0.018). Homelessness led to even greater increases in UC visits (IRR, 1.75; 95% CI, 1.29 to 2.39; P < .001), ED visits (IRR, 4.18; 95% CI, 2.77 to 6.30; P < .001), and hospitalizations (IRR, 3.18; 95% CI, 2.03 to 4.97; P < .001). Suboptimal visit adherence differentially impacted UC and ED visits by housing status, suggesting interaction. Conclusions Increased acute care visit frequency among HUH-PLWH suggests that interventions at these visits may create opportunities to improve care.

TheNorthernApenninesofItalyareaclassicalsiteforstudyingfundamentalissuesinthrustwedges,suchasophioliteformationandemplacement,interplaybetweentectonicsandsedimentation,roleofout-of-sequencethrusting, syn-orogenicversuspost-orogenicextension,alongstrikesegmentation,etc.Accordingly,theNorthernApennines have been extensively studied since more than two centuries ago. Despite the huge amount of available data with different resolution, a 3D comprehensive regional view combining in a modern framework all available surface and subsurface information for contiguous sectors of the chain is still lacking. We performed such an attempt in the area framed between the Taro valley to the north and the northern termination of the Alpi Apuane to the south. The region includes the main morphostructural zones of the North-West Apennines from the Tyrrhenian coast West-Northwest of La Spezia, through the main topographic divide of the Apennines, to the external frontal part of the chain. The area has been investigated through a multidisciplinary approach that integrated: 1) surface geological data collected during the last two decades of structural and stratigraphic field works in the internal as well as external sectors of the chain; 2) subsurface geological data including: a) interpretation of ∼1200 Km of seismic reflection profiles tied to surface geology and b) analysis of 39 boreholes stratigraphies. The construction of two regional NE-SW trending cross-sections (the Levanto-Pontremoli-Parma to the North and the La SpeziaSarzana-North Apuane-Cerreto to the South), connected by the NW-SE trending Taro River-Lunigiana Area-Alpi Apuane composite section, allowed us to illustrate (i) the role of out-of-sequence blind thrusting in the basement, (ii)thepresenceoflowanglenormalfaultinganditsrelationshipswithrecenttoactivehighanglenormalfaulting. BothextensionalandcontractionalsystemshaverelevantimplicationsforthetectonicsoftheNorthernApennines as well as the seismotectonics of the studied region.

The E-W−trending Jabal Qusaybah anticline, at the western termination of the Salakh arch, Oman Mountains, is characterized by a complex fault network that developed in layered Cretaceous carbonates. This network includes NE-SW left-lateral, N-S extensional, and subordinate E-W extensional fault zones. The N-S−striking extensional faults zones are roughly perpendicular to the fold axis and are best developed in the longitudinally bulged central sector of the anticlinal crest. They are likely due to along-strike outer-arc extension associated with positive fault inversion and salt migration. These extensional fault zones are confined within, and locally abut, major NE-SW left-lateral strike-slip fault zones. Extensional fault displacements range between a few decimeters and ∼60 m, whereas the maximum exposed trace lengths range between a few meters and ∼800 m. Narrow (∼1−15-cm-thick) cataclastic fault cores are surrounded by vein-dominated damage zones as thick as tens of meters. Moreover, fault zones show widespread evidence for substantial dilation in the form of (1) dilation breccias, (2) infilling by large columnar calcite crystals and aggregates, and (3) centimeter- to meter-thick veins. Dilation breccias and calcite infillings are primarily localized at fault tips, fault overlaps, and interaction zones between strike-slip and extensional fault segments. Displacement profiles along the N-S−striking extensional fault zones indicate that they are one order of magnitude shorter than values predicted by most published displacement-length scaling laws. By analyzing fault abutting geometries, detailed vein relative chronology, δ13C and δ18O signatures, and fluid inclusion data from calcite veins and calcite fault infillings, we propose a model whereby a deep-seated, regionally sized, left-lateral strike-slip fault system that was active during anticline growth inhibited the lateral propagation of late-stage transversal extensional fault zones. Our findings show that, in this geological setting, the structural position, rather than fault displacement, is the parameter controlling the location of the more dilatants (and permeable) fault segments. Results of the present work suggest that fault intersections may be more useful than fault throw for predicting zones of enhanced vertical fluid flow in structurally complex carbonate reservoirs.

Fault zones are known to play a key role in controlling fluid migration, including hydrocarbons, at local and regional scales. In this contribution physicochemical data from veins are used to document the extent and maintenance of fluid conductivity associated with fault-damage zones in an anticlinal structure occurring in the frontal part of a foreland fold and thrust belt. Migration of fluids during major deformational events has been recorded by several generations of calcite and localized dolomite cementation in veins in marine Cretaceous carbonates of the Jabal Qusaybah Anticline (North Oman). Applying detailed petrographic and paragenetic relations, geochemical analysis (stable carbon and oxygen isotopes, strontium isotopes, and trace elements), and microthermometry, coupled with structural studies of fault zones and associated calcite veins, made it possible to link fluid circulation to the structural evolution of the Jabal Qusaybah Anticline. Based on the structural framework and fault systems, three groups of veins were distinguished. Group 1 veins are interpreted to be linked to burial and early-tectonic deformation in association with E-W extensional fault zones. Calcite cementation in this group occurred in a closed to semiclosed fluid system, which originated as a result of intraformational fluid movement along a low-connectivity fracture network. The delta C-13 values of these veins range from 3% to 3.5%, and delta O-18 values vary from -10.3 to -8.1% V-PDB. Group 2 veins are related to syntectonic deformation along NE-SW strike-slip and incipient N-S extensional faults linked to culmination of the Jabal Qusaybah Anticline. From this stage onward, fluids correspond to progressive fault connectivity and dilation related to interaction of fault-folding systems. The cements precipitated during this stage have more variable delta C-13 values ranging from 0.9 to 3.2% and possess a wide range of delta O-18 values varying between -11.2 and 0.3% V-PDB. The cements in Group 2 veins originated from fluids characterized by a relatively broad range of precipitation temperature (75-107 degrees C) and salinities evolving from seawater to moderately saline fluids (3.4-12.8 eq. wt% NaCl), with H2O-NaCl composition. The source of salinity is inferred to be evaporitic brines that originated from the Ara Group, and the large range of salinity is interpreted as the result of mixing between those brines and modified seawater. Group 3 veins are considered to be related to late-tectonic deformation corresponding to late fold amplification of the anticline hinge, transition from NE-SW left-lateral strike-slip to N-S extensional faulting, progressive regional and local uplift, and exhumation. Stable-isotope data support the occurrence of bacterial methanogenesis or CO2 degassing at the end of this stage. Their associated cements are characterized by higher delta C-13 and delta O-18 values compared to other groups of veins, ranging from 0.6 to 8.0% and -3.6 to 1.5% V-PDB, respectively. Fluids responsible for calcite precipitation in this group evolved from a moderate saline to a more saline (8.5-16 eq. wt. % NaCl) H2O-NaCl-CaCl2 brine. The progressive O-18 enrichment relative to seawater and preceding cements and its covariation with fluid salinity in the later stage suggest the higher contribution of the evaporitic brines. This hypothesis is further supported by the increase in their Sr-87/Sr-86 ratios compared to both middle to Upper Cretaceous marine carbonates and other groups of veins. Although during this episode calcite cementation occurred at temperatures below 50 degrees C, their geochemical signatures reveal that the faults were sufficiently conductive to transfer extraformational fluids late in the deformation history of this structure. The interference between strike-slip and extensional fault systems and their interaction with fold amplification is invoked to be responsible for enhanced conductivity in fault-damage zones.

The links between obesity, inflammation and insulin resistance, which are all key characteristics of type 2 diabetes mellitus, are yet to be delineated in the brain. One of the key neuroinflammatory proteins detected in the hypothalamus with over-nutrition is tumour necrosis factor (TNF)α. Using immortalised embryonic rat and mouse hypothalamic cell lines (rHypoE-7 and mHypoE-46) that express orexigenic neuropeptide Y and agouti-related peptide, we investigated changes in insulin signalling and inflammatory gene marker mRNA expression after TNFα exposure. A quantitative polymerase chain reaction array of 84 inflammatory markers (cytokines, chemokines and receptors) demonstrated an increase in the expression of multiple genes encoding inflammatory markers upon exposure to 100 ng mL-1 TNFα for 4 hours. Furthermore, neurones pre-exposed to TNFα (50 ng mL-1 ) for 6 or 16 hours exhibited a significant reduction in phosphorylated Akt compared to control after insulin treatment, indicating the attenuation of insulin signalling. mRNA expression of insulin signalling-related genes was also decreased with exposure to TNFα. TNFα significantly increased mRNA expression of IκBα, Tnfrsf1a and IL6 at 4 and 24 hours, activating a pro-inflammatory state. An inhibitor study using an inhibitor of nuclear factor kappa B kinase subunit β (IKK-β) inhibitor, PS1145, demonstrated that TNFα-induced neuroinflammatory marker expression occurs through the IKK-β/nuclear factor-kappa B pathway, whereas oleate, a monounsaturated fatty acid, had no effect on inflammatory markers. To test the efficacy of anti-inflammatory treatment to reverse insulin resistance, neurones were treated with TNFα and PS1145, which did not significantly restore the TNFα-induced changes in cellular insulin sensitivity, indicating that an alternative pathway may be involved. In conclusion, exposure to the inflammatory cytokine TNFα causes cellular insulin resistance and inflammation marker expression in the rHypoE-7 and mHypoE-46 neurones, consistent with effects seen with TNFα in peripheral tissues. It also mimics insulin- and palmitate-induced insulin resistance in hypothalamic neurones. The present study provides further evidence that altered central energy metabolism may be caused by obesity-induced cytokine expression.

The brain, specifically the hypothalamus, controls whole body energy and glucose homeostasis through neurons that synthesize specific neuropeptides, whereas hypothalamic dysfunction is linked directly to insulin resistance, obesity, and type 2 diabetes mellitus. Nutrient excess, through overconsumption of a Western or high-fat diet, exposes the hypothalamus to high levels of free fatty acids, which induces neuroinflammation, endoplasmic reticulum stress, and dysregulation of neuropeptide synthesis. Furthermore, exposure to a high-fat diet also disrupts normal circadian rhythms, and conversely, clock gene knockout models have symptoms of metabolic disorders. While whole brain/animal studies have provided phenotypic end points and important clues to the genes involved, there are still major gaps in our understanding of the intracellular pathways and neuron-specific components that ultimately control circadian rhythms and energy homeostasis. Because of its complexity and heterogeneous nature, containing a diverse mix cell types, it is difficult to dissect the critical hypothalamic components involved in these processes. Of significance, we have the capacity to study these individual components using an extensive collection of both embryonic- and adult-derived, immortalized hypothalamic neuronal cell lines from rodents. These defined neuronal cell lines have been used to examine the impact of nutrient excess, such as palmitate, on circadian rhythms and neuroendocrine signaling pathways, as well as changes in vital neuropeptides, leading to the development of neuronal inflammation; the role of proinflammatory molecules in this process; and ultimately, restoration of normal signaling, clock gene expression, and neuropeptide synthesis in disrupted states by beneficial anti-inflammatory compounds in defined hypothalamic neurons.

Housing instability negatively impacts outcomes in people living with human immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has not previously been evaluated. Using 6 dwelling types to measure housing status, we found a strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements.

© 2018 Jason Coquim et al. This investigation assessed the biomechanical performance of the metal plate and bone strut technique for fixing recalcitrant nonunions of femur midshaft segmental defects, which has not been systematically done before. A finite element (FE) model was developed and then validated by experiments with the femur in 15 deg of adduction at a subclinical hip force of 1 kN. Then, FE analysis was done with the femur in 15 deg of adduction at a hip force of 3 kN representing about 4 x body weight for a 75 kg person to examine clinically relevant cases, such as an intact femur plus 8 different combinations of a lateral metal plate of fixed length, a medial bone strut of varying length, and varying numbers and locations of screws to secure the plate and strut around a midshaft defect. Using the traditional “high stiffness” femur-implant construct criterion, the repair technique using both a lateral plate and a medial strut fixed with the maximum possible number of screws would be the most desirable since it had the highest stiffness (1948 N/mm); moreover, this produced a peak femur cortical Von Mises stress (92 MPa) which was below the ultimate tensile strength of cortical bone. Conversely, using the more modern “low stiffness” femur-implant construct criterion, the repair technique using only a lateral plate but no medial strut provided the lowest stiffness (606 N/mm), which could potentially permit more in-line interfragmentary motion (i.e., perpendicular to the fracture gap, but in the direction of the femur shaft long axis) to enhance callus formation for secondary-type fracture healing; however, this also generated a peak femur cortical Von Mises stress (171 MPa) which was above the ultimate tensile strength of cortical bone.

Classical frictional fault reactivation models indicate that slip along misoriented fault planes is not possible under most conditions. Nevertheless, active or exhumed low-angle normal faults have been described in many settings worldwide. This discrepancy is addressed by contrasting models: (1) those proposing that low-angle normal faults result from postkinematic passive rotation of former high-angle extensional faults; and (2) those proposing that specific conditions can promote slip along misoriented fault planes. This paper describes the Tellaro detachment, a mid–late Miocene low-angle normal fault that was responsible for ∼500 m of tectonic vertical thinning in the carbonate-dominated Triassic to Lower Miocene succession of the Northern Apennines, Italy. By integrating structural, petrographic, isotopic, and fluid inclusion data, we show that: (1) the main kinematic activity of the Tellaro detachment occurred between ∼8 and 4 km depths and peak temperature ∼190 °C; (2) dilational breccias, tens of cubic meters in volume, are frequently associated with major low-angle fault segments; (3) slip along misoriented planes was favored by elevated fluid pressures and low differential stress; and (4) the fault system was characterized by transient permeability pulses and overpressure buildups, associated with multiple fracturing and cementation events that caused the downward migration of master slip surfaces. Results presented in this study show that: (1) in a fluid-active regime, continental crustal thinning can occur for shallow values of fault dip; (2) low-angle normal faults have a great influence on fluid circulation within the upper crust; and (3) episodic permeability enhancement and destruction in detachment faults can promote overpressure buildups, triggering deformation episodes.

The Jabal Qusaybah anticline is located at the western end of the Salakh Arch, a major salient in the foothills of the Oman Mountains. We performed a structural and petrographical-geochemical study of vein sets and fault zones associated with the development of this anticline. Our data illustrate a complex deformation pattern both in space and time, characterized by the unusual presence of widespread NE-SW left-lateral strike-slip fault zones trending oblique to the E-W fold axial strike, and of abundant and well-developed N-S fold-perpendicular extensional fault zones associated with axial bulging and dilation, well developed in the central region of the anticlinal crest. We propose a three-stage evolution for the Jabal Qusaybah anticline, starting with prefolding jointing in the foreland of the late Cretaceous Oman Mountains, and followed by development of extensional faulting in Campanian times. Positive inversion of the Qusaybah Fault, possibly in Miocene times, caused development of a layer-parallel shortening fabric and amplification the Jabal Qusaybah Anticline, in concomitance with the activity of NE-SW left-lateral strike-slip fault zones that triggered N-S, fold-perpendicular extensional faulting, particularly in the axial bump of the anticline. The final evolutionary stage was characterized by further amplification of the axial bump and related N-S extensional fracturing and by uplift and exhumation. To explain the complex noncylindrical fault-fold interactions in the study anticline, we tentatively propose that they were triggered by near foredeep-parallel tapering of the sedimentary/tectonic overburden of the Ara evaporites.

Background: Lower thermal and discomfort thresholds may predispose multiple sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia (FM) comorbidity has never been investigated. Aims were to investigate the thermal and discomfort thresholds in the evaluation of pain intensity between MS patients with FM (PFM+) and MS patients with pain not associated to FM (PFM−). Methods: One hundred thirty three MS patients were investigated for chronic pain. FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was used to measure the thresholds in the patients and 60 matched healthy subjects. Results: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM−. PFM+ were predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no other significant differences emerged than PFM−. The thresholds were lower in MS patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the thermal threshold (p < 0.001), while the female gender influenced the discomfort threshold (p < 0.001). Conclusion: Thermal and discomfort thresholds were lower in patients than controls and were the lowest in PFM+. Their more severely impaired thermal threshold supports a neurophysiological basis of such association.

Background Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. Methods Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. Results 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0–8.5) and mean disease duration of 10.3 years (range 1–50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20–63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. Conclusions Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

The Vado di Corno Fault Zone (VCFZ) is an active extensional fault cutting through carbonates in the Italian Central Apennines. The fault zone was exhumed from ∼2 km depth and accommodated a normal throw of ∼2 km since Early-Pleistocene. In the studied area, the master fault of the VCFZ dips N210/54° and juxtaposes Quaternary colluvial deposits in the hangingwall with cataclastic dolostones in the footwall. Detailed mapping of the fault zone rocks within the ∼300 m thick footwall-block evidenced the presence of five main structural units (Low Strain Damage Zone, High Strain Damage Zone, Breccia Unit, Cataclastic Unit 1 and Cataclastic Unit 2). The Breccia Unit results from the Pleistocene extensional reactivation of a pre-existing Pliocene thrust. The Cataclastic Unit 1 forms a ∼40 m thick band lining the master fault and recording in-situ shattering due to the propagation of multiple seismic ruptures. Seismic faulting is suggested also by the occurrence of mirror-like slip surfaces, highly localized sheared calcite-bearing veins and fluidized cataclasites. The VCFZ architecture compares well with seismological studies of the L'Aquila 2009 seismic sequence (mainshock M W 6.1), which imaged the reactivation of shallow-seated low-angle normal faults (Breccia Unit) cut by major high-angle normal faults (Cataclastic Units).

L’articolo fornisce i primi dati di una ricerca in corso sulle comunità di stranieri immigrati residenti nella provincia di Viterbo e sulla partecipazione a corsi di lingua italiana offerti, autonomamente o in appoggio alle strutture pubbliche, dalle associazioni di volontariato inserite nella rete “Scuolemigranti”. La mappatura, realizzata per la prima volta e aggiornata tramite il confronto con i dati statistici nazionali e regionali, consente di apprezzare il rilievo quantitativo dell’immigrazione nel Viterbese e il suo impatto sociolinguistico sul territorio, con particolare riguardo alla presenza di studenti stranieri nella scuola. Uno specifico approfondimento è dedicato all’analisi di uno dei manuali usati nella didattica dell’italiano L2 ad adulti, e nel paragrafo conclusivo si presenta un progetto didattico in corso di realizzazione in classi plurilingui di scuole primarie e medie di primo grado della provincia di Viterbo. Teaching Italian to immigrants in Viterbo: initial notes This paper introduces the initial results of a study currently being carried out on immigrant families residing in the province of Viterbo (Northern Latium), especially focused on Italian language classes (A1-A2 levels) offered by the “Scuolemigranti” Volunteer Network either independently or as a support to the National Education Curriculum. After creating a statistical survey, which is updated using national and regional data, this study highlights the resident migrant population in the area and aims to show how the Viterbo sociolinguistic community is affected by an intensive migration flow. In the first section, the scientific and juridical backgrounds are outlined, then national and regional migration statistics are examined, principally focusing on school populations, addressing the features of an Italian language textbook for adult Italian L2 learners. Finally a teaching project on writing skills within multilingual classes in primary and middle schools in the province of Viterbo is presented., Italiano LinguaDue, Vol 8, No 2 (2016)

Background: Robotic training is commonly used to assist walking training in patients affected by multiple sclerosis (MS) with non-conclusive results. Objective: To compare the effect of robot-assisted gait training (RAGT) with that of conventional walking training (CWT) on gait competencies, global ability, fatigue and spasticity in a group of severely affected patients with MS. Methods: A pilot, single-blind randomized controlled trial was conducted in 43 severe (Expanded Disability Status Scale (EDSS) score of 6–7.5) and non-autonomous ambulant in-patients with MS. Experimental group performed 12 sessions of RAGT, whereas control group performed the same amount of CWT. Primary outcome measures were gait ability assessed by 2 minutes walking test and Functional Ambulatory Category; secondary outcomes were global ability (modified Barthel Index), global mobility (Rivermead Mobility Index), severity of disease (EDSS) and subjectively perceived fatigue (Fatigue Severity Scale). Results: The number of subjects who achieved a clinical significant improvement was significantly higher in RAGT than in CWT ( p Conclusions: RAGT improved the walking competencies in non-autonomous ambulant patients with MS, with benefits in terms of perceived fatigue.

Background Chronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients' health-related quality of life (HRQoL). Material and methods 133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales. Results Chronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM-); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL. Conclusions In our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients' QoL.

Background Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes in patients with S. aureus bacteremia. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies. To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes. Methods We conducted an observational study (n = 32) to evaluate the prognostic value of circulating protein biomarkers for mortality and persistent bacteremia in patients with S. aureus bloodstream infections. A case–control study of 124 patients with complicated confirmed S. aureus bloodstream infections was used to validate our findings in the observational study. Results We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia by multiple comparisons. Further statistical modeling identified IL-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers having the best power to classify fatal outcome. Baseline IL-17A levels were elevated in patients with persistent bacteremia, endovascular and metastatic tissue infections. Conclusion The results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials. Disclosures All authors: No reported disclosures.

Background: We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. Methods: By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1-60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. Results: Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1-57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7-60). Worsening occurred 1-24 months (median 4.5) after IVIg discontinuation and 1-31 months (median 14) after IVMP discontinuation (p=0.0126). Conclusions: A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP.

Despite established standards, effective treatments, and evidence-based guidelines, postoperative pain control in Italy and other parts of the world remains suboptimal. Pain control has been recognized as a fundamental human right. Effective treatments exist to control postsurgical pain. Inadequate postoperative analgesia may prolong the length of hospital stays and may adversely impact outcomes.The same multiple-choice survey administered at the SIAARTI National Congress in Perugia in 2006 (n=588) was given at the SIAARTI National Congress in Naples, Italy in 2012 (n=635). The 2012 survey was analysed and compared to the 2006 results.Postoperative pain control in Italy was less than optimal in 2006 and showed no substantial improvements in 2012. Geographical distinctions were evident with certain parts of Italy offering better postoperative pain control than other. Fewer than half of hospitals represented had an active Acute Pain Service (APS) and only about 10% of postsurgical patients were managed according to evidence-based guidelines. For example, elastomeric pumps for continuous IV infusion are commonly used in Italy, although patient-controlled analgesia systems are recommended in the guidelines. The biggest obstacles to optimal postoperative pain control reported by respondents could be categorized as organizational, cultural, and economic.There is considerable room for improvement in postoperative pain control in Italy, specifically in the areas of clinical education, evidence-based treatments, better equipment, and implementation of active APS departments in more hospitals. Two surveys taken six years apart in Italy reveal, with striking similarity, that there are many unmet needs in postoperative pain control and that Italy still falls below European standards for postoperative pain control.