Infrared spectroscopy of serum as a potential diagnostic screening approach for naturally occurring canine osteoarthritis associated with cranial cruciate ligament rupture.

OBJECTIVE: To evaluate infrared (IR) spectroscopy of serum as a screening tool to differentiate dogs affected by naturally occurring osteoarthritis (OA) associated with cranial cruciate ligament rupture (CrCLR) and controls. METHOD: 104 adult dogs with CrCLR (affected group) and 50 adult control dogs were recruited for this prospective observational study. Serum samples were collected preoperatively from CrCLR dogs and from a subset of these dogs at 4-, and 12-week post-surgical intervention to stabilize the affected stifles. Serum was collected once from control dogs. Dry films were made from serum samples, and IR absorbance spectra acquired. Data preprocessing, principal component analysis and multivariate analysis of covariance were performed to separate samples from the two groups, and to evaluate temporal differences. Weighted logistic regression with L1 regularization method was used to develop a predictive model. Model performance based on an independent test set was evaluated. RESULTS: Spectral data analysis revealed significant separation between the sera of CrCLR and control dogs (P < 0.0001), but not amongst different time points in the OA group. The sensitivity, specificity, AUC and accuracy of the test set were 84.62%, 96.15%, 93.20% and 92.31% respectively. CONCLUSIONS: These findings confirm the potential of IR-spectroscopy of serum with chemometrics methods to differentiate controls from dogs with OA associated with CrCLR. This is the first step in development of an economic, and comparatively simple IR-based screening serum test for OA. Utility of this tool as a clinical screening and diagnostic test requires further investigation and validation.

Promising Role of Toll-Like Receptor 8 Agonist in Concert with Prostratin for Activation of Silent HIV.

The persistence of latently HIV-infected cells in patients under combined antiretroviral treatment (cART) remains the major hurdle for HIV eradication. Thus far, individual compounds have not been sufficiently potent to reactivate latent virus and guarantee its elimination in vivo. Thus, we hypothesized that transcriptional enhancers, in concert with compounds triggering the innate immune system, are more efficient in reversing latency by creating a Th1 supportive milieu that acts against latently HIV-infected cells at various levels. To test our hypothesis, we screened six compounds on a coculture of latently infected cells (J-lat) and monocyte-derived dendritic cells (MDDCs). The protein kinase C (PKC) agonist prostratin, with a Toll-like receptor 8 (TLR8) agonist, resulted in greater reversion of HIV latency than any single compound. This combinatorial approach led to a drastic phenotypic and functional maturation of the MDDCs. Tumor necrosis factor (TNF) and cell-cell interactions were crucial for the greater reversion observed. Similarly, we found a greater potency of the combination of prostratin and TLR8 agonist in reversing HIV latency when applying it to primary cells of HIV-infected patients. Thus, we demonstrate here the synergistic interplay between TLR8-matured MDDCs and compounds acting directly on latently HIV-infected cells, targeting different mechanisms of latency, by triggering various signaling pathways. Moreover, TLR8 triggering may reverse exhaustion of HIV-specific cytotoxic T lymphocytes that might be essential for killing or constraining the latently infected cells. IMPORTANCE: Curing HIV is the Holy Grail. The so-called "shock and kill" strategy relies on drug-mediated reversion of HIV latency and the subsequent death of those cells under combined antiretroviral treatment. So far, no compound achieves efficient reversal of latency or eliminates this latent reservoir. The compounds may not target all of the latency mechanisms in all latently infected cells. Moreover, HIV-associated exhaustion of the immune system hinders the efficient elimination of the reactivated cells. In this study, we demonstrated synergistic latency reversion by combining agonists for protein kinase C and Toll-like receptor 8 in a coculture of latently infected cells with myeloid dendritic cells. The drug prostratin stimulates directly the transcriptional machinery of latently infected cells, and the TLR8 agonist acts indirectly by maturing dendritic cells. These findings highlight the importance of the immune system and its activation, in combination with direct-acting compounds, to reverse latency.

[What is new in 2014 for the specialist in hospital internal medicine? The point of view of university hospital chief residents]. / L'année 2014 mise en perspective par les internistes hospitaliers.

The year 2014 was rich in significant advances in all areas of internal medicine. Many of them have an impact on our daily practice and on the way we manage one problem or another. From the use of the ultrasound for the diagnosis of pneumonia to the choice of the site of venous access and the type of line, and the increasing complexity of choosing an oral anticoagulant agent, this selection offers to the readers a brief overview of the major advances. The chief residents in the Service of internal medicine of the Lausanne University hospital are pleased to share their readings.

Intermittent operation of QC-lasers for mid-IR spectroscopy with low heat dissipation: tuning characteristics and driving electronics.

Intermittent scanning for continuous-wave quantum cascade lasers is proposed along with a custom-built laser driver optimized for such operation. This approach lowers the overall heat dissipation of the laser by dropping its drive current to zero between individual scans and holding a longer pause between scans. This allows packaging cw-QCLs in TO­3 housings with built-in collimating optics, thus reducing cost and footprint of the device. The fully integrated, largely analog, yet flexible laser driver eliminates the need for any external electronics for current modulation, lowers the demands on power supply performance, and allows shaping of the tuning current in a wide range. Optimized ramp shape selection leads to large and nearly linear frequency tuning (>1.5 cm−1). Experimental characterization of the proposed scheme with a QCL emitting at 7.7 µm gave a frequency stability of 3.2×10−5 cm−1 for the laser emission, while a temperature dependence of 2.3×10−4 cm−1/K was observed when the driver electronics was exposed to sudden temperature changes. We show that these characteristics make the driver suitable for high precision trace gas measurements by analyzing methane absorption lines in the respective spectral region.

Reference equations for ultrasound bone densitometry of the radius in Central European children and adolescents.

UNLABELLED: Bone density measurements are important for evaluation and follow-up of children with alterations in their mineral status (increased risk for fractures and osteoporosis subsequently). Interpretation of these measurements relies on the availability of appropriate reference equations. We developed gender-specific, age-dependent reference values of bone density for Central European children. INTRODUCTION: In recent years, there has been an increasing demand for the measurement of bone density in children exposed to an increased risk of early alterations in their bone status. These values must be compared to an adequate reference population. The aim of the present study was to create reference equations of radial speed of sound (SOS) for Central European children and adolescents. METHODS: In this cross-sectional study, SOS values were measured at the distal third of the radius in 581 Swiss children and adolescents (321 girls and 260 boys) aged 6 to 16 years using the Sunlight Omnisense® 7000P quantitative ultrasound system. RESULTS: Gender-specific reference equations for SOS values were derived by polynomial regression and combined a cubic dependence of age and a linear dependence of height. The fitted SOS curves in our study population show a plateau period in both genders for younger ages followed by an increase phase beginning at the age of 12 in girls and 14 in boys. Neither the reported level of physical activity nor additional sport nor self-reported calcium intake influenced the reference equations. CONCLUSIONS: Our results show a good agreement with similar studies using the same measurement technique on other body parts, suggesting a wide applicability of the obtained reference curves over different European populations.

[What is new in 2012 for the specialist in hospital internal medicine?]. / L'année 2012 de la perspective de l'interniste hospitalier.

The knowledge in internal medicine is constantly and so rapidly evolving that practices have to be updated and adjusted to recent scientific rules, in order to improve quality and efficiency in the day to day activities. Residents in the Service of internal medicine of the Lausanne University present several relevant papers published in 2012, whose results are susceptible to change the daily hospital practices. From modest impacts to real revolution, a variety of subjects are discussed in the perspective of evidence based medicine.

[Therapeutic and clinical implications of elevated levels of vitamin B12]. / Hypervitaminémie B12: implications cliniques et prise en charge.

In general practice, vitamin B12 levels are measured when searching an origin for an anemic status (usually megaloblastic anemia), for various neurological disorders (usually polyneuropathy) or for neurocognitive disorders. Although the pathologies associated with vitamin B12 deficiency are well known, hypervitaminemic B12 status is often fortuitous and frequent finding. The aim of this article is to present the disease entities associated with hypervitaminemia B12, the clinical implications of this dysvitaminosis and a practical approach when this laboratory abnormality is found.

[Hospital-based internal medicine: year 2011 in chief resident's perspective]. / Médecine interne générale en pratique hospitalière: l'année 2011 mise en perspective par les chefs de clinique.

The year 2011 was full of significant advances in all areas of medicine. Whether small or large issues, they all have an impact on daily practice in general internal medicine. For example, intravenous administration of diuretics in heart failure shows no benefit. But double dose may improve symptoms faster. Direct Xa inhibitors are emerging as alternative to anti-vitamin K. beta-blockers reduce overall mortality in COPD and do not worsen lung function significantly. Each year, the chief residents from the Department of internal medicine at the University hospital of Lausanne meet to share their readings. Twelve new therapeutic considerations of 2011 are reviewed here.

When pliers become fingers in the monkey motor system.

The capacity to use tools is a fundamental evolutionary achievement. Its essence stands in the capacity to transfer a proximal goal (grasp a tool) to a distal goal (e.g., grasp food). Where and how does this goal transfer occur? Here, we show that, in monkeys trained to use tools, cortical motor neurons, active during hand grasping, also become active during grasping with pliers, as if the pliers were now the hand fingers. This motor embodiment occurs both for normal pliers and for "reverse pliers," an implement that requires finger opening, instead of their closing, to grasp an object. We conclude that the capacity to use tools is based on an inherently goal-centered functional organization of primate cortical motor areas.

Quantitative analysis of the intramedullary arterial supply of the feline tibia.

OBJECTIVES: To quantitatively describe the intramedullary arterial supply of the adult feline tibia and determine if the arterial supply is significantly different from that of adult small dogs. METHODS: Cadaveric feline and canine pelvic limbs were obtained to prospectively investigate the intramedullary arterial supply of the tibia. A microvascular injection and modified Spalteholz bone clearing technique were used to characterize and quantify the intramedullary arterial supply of the tibia. Statistical comparisons were made between cats and dogs for the percentage of intramedullary arterial supply (arterial density) and the diameter of the nutrient artery. RESULTS: No significant difference was observed in the intramedullary arterial density between dog and cat tibiae. The feline nutrient artery diameter (0.55 ± 0.1 mm) was significantly greater than the canine nutrient artery (0.30 ± 0.04 mm) in the distal section of bone. Dogs subjectively had a greater number of branching vessels in the distal and mid-diaphyseal sections of bone when compared to cats. CLINICAL SIGNIFICANCE: Delayed fracture healing in the feline tibia does not appear to be associated with a lack of intramedullary arterial supply. A lack of diffuse arborization of the arterial supply to the middle and distal feline tibia may explain, at least in part, why feline tibial delayed or nonunions may be more common than in canine tibial fractures.

Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood.

BACKGROUND: Recent studies indicate that prenatal vitamin D intake may protect against the development of atopic diseases in young children. Vitamin D has been shown to induce tolerogenic antigen-presenting cells such as dendritic cells. Whether the allergy-protective potential of prenatal vitamin D is mediated through such mechanisms is, however, unknown. OBJECTIVE: To evaluate the association between prenatal vitamin D supplementation and tolerogenic antigen-presenting cells in cord blood (CB) as determined by mRNA measurement of immunoglobulin-like transcripts (ILT)3 and ILT4. METHODS: A prospective multi-centre birth cohort was established in rural areas of five European countries. Information on maternal exposures including vitamin D intake was collected by questionnaires during pregnancy. The gene expression of ILT3 and ILT4 was analysed by real-time PCR in the CB of 927 children. Maternal vitamin D supplementation was assessed in Finland and France (n=349). RESULTS: Maternal vitamin D supplementation during pregnancy was associated with an increase in the gene expression of ILT3 (P=0.012) and ILT4 (P<0.001). This association remained significant for ILT4 (P=0.020) and showed a positive trend for the gene expression of ILT3 (P=0.059) after multivariate analysis controlling for various confounders. CONCLUSIONS: Vitamin D supplementation during pregnancy may increase the mRNA levels of ILT3 and ILT4 in CB. This finding may point towards an early induction of tolerogenic immune responses by maternal vitamin D intake.

An in vitro mechanical comparison of tibial plateau levelling osteotomy plates.

An in vitro mechanical study was performed to compare the fatigue properties and the loads to failure of four plate designs that are used to stabilise the tibial plateau levelling osteotomy (TPLO). Seventy-two gapped osteotomy models were created using 3.5 mm versions of the following plates: a standard TPLO plate, a low profile TPLO plate, a locking TPLO plate (LocP), and a broad locking TPLO plate (bLocP). The 18 constructs for each plate design were sub-divided into three identical groups of six. Six constructs were mounted in a materials testing device and subjected to cyclic compressive loading until failure was observed or one-million cycles were achieved. Additionally, six constructs of each plate design were tested in compressive axial loading and six others in four-point bending in a load-to-failure manner. To provide residual strength comparisons, the six constructs undergoing cyclic fatigue compression testing were also tested in axial compressive loading. There were not any significant differences in stiffness between plates tested in axial compressive loading. However, mean loads at failure were higher for the LocP and bLocP constructs. The bLocP had a significantly higher mean stiffness and mean load at failure compared to the other constructs tested in four-point bending.

Reference equations for lung function screening of healthy never-smoking adults aged 18-80 years.

The need for updated spirometric reference values to be used on European populations is widely acknowledged, especially for subjects aged >70 yrs. Their reference values are generally based on extrapolations. The aim of the present study was to calculate reference values for lung function screening of healthy, never-smoking adults aged 18-80 yrs and to compare them with the most widely used reference equations. Results of screening spirometry of 8,684 healthy, never-smoking adults were used to calculate mean values and fifth percentiles of lung function variables. The European Community of Coal and Steel (ECCS) reference equations underestimate forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). For example, in 50-yr-old males (height 175 cm), lower limits of normal for FEV(1) are underestimated by 198 mL, and for FVC by 210 mL. In 50-yr-old females (height 165 cm), lower limits of normal for FEV(1) are underestimated by 191 mL, and for FVC by 270 mL. The decline of FVC in elderly subjects is steeper than predicted by the ECCS. Reference equations derived from spirometry data locally collected in a practical setting by well-trained personnel might be more appropriate for everyday use than generally used equations based on data from scientific studies in the distant past.

Shear wave elastography safety in fetus: A quantitative health risk assessment.

PURPOSE: To identify the effects of shear wave elastography in the fetus for evaluation in widespread use. MATERIALS AND METHODS: The Health Risk Assessment method proposed by the National Research Council was used with literature to evaluate the safety of shear wave elastography for the fetus regarding its potential effects in human tissues. RESULTS: The experimental and epidemiologic data from 25 articles showed that shear wave elastography maintained the same thermal effect as pulsed Doppler ultrasound already authorized in obstetrics, and that cavitation effect on fetal tissue is improbable. Nonetheless, the vibratory character of shear waves could induce displacement of fetal tissue while potential effects of very short duration energy peaks of the radiation force focused wave front remain unknown. CONCLUSION: The actual knowledge does not provide enough information to assess the effects of shear wave elastography on fetal tissues, thus these points have to be explored by further experimental studies.

Stiffness of modified Type 1a linear external skeletal fixators.

Modifications of a Type 1a external skeletal fixator (ESF) frame were evaluated by alternately placing transfixation pins on opposite sides of the connecting rod (Type 1a-MOD) or by placing additional connecting rods on either of the two inside (Type 1a-INSIDE) or two outside (Type 1a-OUTSIDE) transfixation pins. The objective of this study was to evaluate the stiffness of these modifications in terms of axial compression (AC), cranial-caudal bending (CCB), and medial-lateral bending (MLB). We hypothesized that these designs would allow significant increase in unilateral frame stiffness, over Type 1a, without proportional increase in frame complexity or technical difficulty of application. All of the ESF frames were constructed using large IMEX SKtrade mark clamps, 3.2 mm threaded fixation pins, 9.5 mm carbon fibre connecting rods and Delrin rods as bone models. Nine, eight pin frames of each design were constructed, and subjected to repetitive non-destructive loading forces (AC, CCB, MLB) using a materials testing machine. Frame construct stiffness for each force (AC, CCB, MLB) was derived from load-deformation curve analysis and displayed in N/mm. Data revealed the 1a-MOD and 1a-OUTSIDE constructs had significantly increased stiffness in CCB and AC as compared to the Type 1a constructs while all of the modified constructs were significantly stiffer in MLB than the Type 1a constructs.

Intended and actual use of self-medication and alternative products during pregnancy by French women.

OBJECTIVES: (i) To identify the proportion of non-pregnant women intending to use self-medication and self-administered alternative products (dietary supplements, essential oils and herbal teas) in the event of pregnancy, and the proportion of pregnant women using these products. (ii) To describe women's risk perception related to these products and the advice given by health professionals. METHODS: A cross-sectional study was conducted. One hundred and twenty-eight women (60 non-pregnant and 68 pregnant women) responded to a self-administered questionnaire. RESULTS: The proportion of pregnant women using self-medication was higher than the proportion of non-pregnant women intending to use self-medication (72% vs 48%, P=0.01) and lower for the use of herbal teas (29% vs 63%, P<0.01). There were no differences between the two groups for dietary supplements (25%) and essential oils (18%). Non-prescribed medications were perceived as a risk by 90% of all the women. Dietary supplements were considered as a medication by 68% of pregnant women and 48% of non-pregnant women (P=0.04). Health professionals provided advice for alternative products to 23% of the pregnant women, and 83% of the non-pregnant women expressed the wish to receive advice if they became pregnant. CONCLUSION: Health professionals should inform women, even before pregnancy, about the safe use of medications and alternative products during pregnancy.

TNF-alpha enhances intracellular glucocorticoid availability.

For understanding the mechanism(s) relating inflammation to corticosteroid action, the effect of tumour necrosis factor-alpha (TNF-alpha) on 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme regulating access of 11beta-hydroxycorticosteroids to receptors, was studied in LLC-PK(1) cells. We observed (i) NAD-dependent enzyme activity and mRNA for 11beta-HSD2, but not 11beta-HSD1, (ii) increasing 11beta-HSD2 activity with increasing degree of differentiation and (iii) a concentration-dependent down-regulation by TNF-alpha, phorbol myristate acetate (PMA) or glucose of activity and mRNA of 11beta-HSD2. The decrease of activity and mRNA by glucose and PMA, but not that by TNF-alpha, was abrogated by the protein kinase C inhibitor GF-109203X. The effect of TNF-alpha on 11beta-HSD2 was reversed by inhibiting the mitogen-activated protein kinases ERK with PD-098050 and p38 by SB-202190, or by activating protein kinase A with forskolin. Overexpression of MEK1, an ERK activator, down-regulated the 11beta-HSD2 activity. In conclusion, TNF-alpha decreases 11beta-HSD2 activity and thereby enhances glucocorticoid access to glucocorticoid receptors to modulate the inflammatory response.

Chemical sensing with pulsed QC-DFB lasers operating at 15.6 micrometers.

Pulsed thermoelectrically cooled QC-DFB lasers operating at 15.6 micrometers were characterized for spectroscopic gas sensing applications. A new method for wavelength scanning based on repetition rate modulation was developed. A non-wavelength-selective pyroelectric detector was incorporated in the sensor configuration giving the advantage of room-temperature operation and low cost. Absorption lines of CO2 and H2O were observed in ambient air, providing information about the concentration of these species.

Natural history of a hamstring tendon autograft used for anterior cruciate ligament reconstruction in a sheep model.

The purpose of this study was to describe the histologic structure of the intraarticular segment of a semitendinosus tendon autograft used for anterior cruciate ligament reconstruction over the first year after surgery. We performed an anterior cruciate ligament reconstruction in a single hindlimb of 11 sheep using a doubled semitendinosus tendon autograft secured to the femur with an endoscopic button and polyester tape and to the tibia with sutures tied around a screw. The histologic structure of the intraarticular segment of the graft at 4, 8, 12, 24, and 52 weeks after surgery was compared with that of the normal semitendinosus tendon and anterior cruciate ligament. The random collagen fiber orientation progressed to a longitudinal orientation from the peripheral to the central areas of the graft over the initial 12 weeks after surgery. A uniform sinusoidal crimp pattern similar to that seen in the normal anterior cruciate ligament was identified under polarized light in nearly one-half of each graft by 24 weeks. Further maturation was noted at 52 weeks. Graft necrosis was not evident at any time period. This study showed that semitendinosus tendon autografts transform into a histologic structure similar to that of the normal anterior cruciate ligament over the initial year after surgery, as has been described for patellar tendon grafts.

Priapism: a review.

Priapism is persistent penile erection in the absence of sexual stimulation. The pattern of blood flow to the penis that occurs during normal erection is altered so that sustained priapism may result in edema, increased risk of abrasion, tissue drying and necrosis of the penis. Numerous causes have been reported in animals and humans. The prognosis depends on the type of priapism and the amount of time that passes before therapeutic intervention. Surgical methods, such as aspiration and shunting procedures, have traditionally been used to treat priapism but carry a risk of postsurgical complications. Use of alpha-agonists for treatment of priapism in humans is often successful and avoids the risks of impotence and other surgical complications. Investigation of the use of alpha-agonists for treatment of priapism in animals should be considered.