Multiprotease improves amino acid release in vitro, energy, and nutrient utilization in broilers fed diets varying in crude protein levels.

Low crude protein (CP) diets can reduce nitrogen (N) excretion and costs by increasing N utilization efficiency. Exogenous proteases may further improve protein digestibility in low CP diets. This study first evaluated in vitro the efficacy of a multiprotease on amino acid (AA) release from feedstuffs and broiler feed. Later, a broiler study evaluated the effect of feeding corn-soybean meal diets containing 3 CP levels (17, 19, and 21% CP) with supplementation on top of 0 or 2,400 U/kg multiprotease on chicken growth performance, total tract CP, and ileal AA digestibilities, and energy utilization. Ross 708 male chickens were placed in 42 cages and assigned to 6 treatments resulting from a 3 × 2 factorial arrangement. Three isocaloric basal diets were formulated to reduce CP, but all diets maintained digestible Lys:CP in 5.47% and the same ideal protein profile. Data were analyzed in a completely randomized design. On average, the multiprotease increased (P < 0.05) in vitro free AA release by 27.81% in most feedstuffs evaluated compared to the control. For broiler feed, 1,200 U/g multiprotease addition improved (P < 0.001) in vitro free AA release by 18.90%. This multiprotease showed interaction effects (P < 0.05) on chicken FCR, energy, and CP digestibility. As expected, BW at 24 d, BW gain, and FCR (8-24 d) worsened (P < 0.001) as dietary CP reduced from 21 to 17%, and multiprotease addition did not improve (P > 0.05) these parameters. BW gain decreased by 12.9% when N intake was reduced from 49.32 to 38.49 g/bird. Multiprotease supplementation improved (P < 0.01) AMEn by 71 kcal/kg, CP digestibility from 59.45 to 63.51%, ileal AA digestibility, and DM digestibility from 67.08 to 73.49%, but only in the 21% CP diet. No differences in ileal AA digestibility due to CP level (P > 0.05) were detected, except for Cys digestibility (P < 0.01). In conclusion, low CP diets reduced growth performance and improved N utilization but negatively affected energy utilization efficiency. Exogenous multiprotease supplementation improved AME, AMEn, protein, ileal AA, and DM digestibility in the 21% CP diet without significantly affecting growth performance.

Effects of corn hardness and drying temperature on digestibility of energy and nutrients in diets fed to growing pigs.

Two experiments were conducted to test the hypothesis that corn kernel hardness and drying temperature influence the ileal digestibility of starch and amino acids (AA), as well as apparent total tract digestibility (ATTD) of gross energy (GE) and total dietary fiber (TDF) in diets for growing pigs. Two corn varieties with average or hard endosperm were grown and harvested under similar conditions, and after harvest, each variety was divided into 2 batches that were dried at 35 and 120 °C, respectively. Therefore, four batches of corn were used. In experiment 1, 10 pigs (67.00 ±â€…2.98 kg) with a T-cannula installed in the distal ileum were allotted to a replicated 5 × 5 Latin square design with 5 diets and 5 periods giving 10 replicates per diet. A nitrogen-free diet and four diets containing each source of corn as the only AA source were formulated. Results indicated that neither variety of corn nor drying temperature influenced apparent ileal digestibility of starch in the grain. The standardized ileal digestibility of most AA was less (P < 0.05) in corn dried at 120 °C compared with corn dried at 35 °C resulting in concentrations of most standardized ileal digestible AA being less (P < 0.05) in corn dried at 120 °C than in corn dried at 35 °C. In experiment 2, 40 pigs (20.82 ±â€…1.74 kg) were housed in metabolism crates and allotted to 4 diets with 10 replicate pigs per diet. The four corn-based diets used in experiment 1 were also used in experiment 2. Feces and urine were collected using the marker-to-marker approach with 5-d adaptation and 4-d collection periods. Results indicated that diets containing hard endosperm corn had greater (P < 0.05) ATTD of TDF than diets containing average endosperm corn. The ATTD of GE in hard endosperm corn was also greater (P < 0.05), and concentrations of digestible energy and metabolizable energy in hard endosperm corn were greater (P < 0.01) than in average endosperm corn. Diets containing corn dried at 120 °C had greater (P < 0.05) ATTD of TDF compared with diets containing corn dried at 35 °C; however, drying temperature did not influence the ATTD of GE. In conclusion, endosperm hardness did not influence the digestibility of AA and starch; however, drying corn at 120 °C reduced digestible AA concentrations. Hard endosperm corn had greater ATTD of GE and TDF, but drying temperature did not influence energy digestibility.

Drying temperatures and corn varieties that inherently differ in kernel hardness, virtuousness, and protein solubility index may influence nutrient digestibility in corn. However, information about interactive effects of corn source (i.e., endosperm hardness) and drying method on nutrient digestibility is limited. Therefore, two experiments were conducted to test the hypothesis that corn source and drying temperature influence energy and nutrient digestibility in corn. Two corn varieties (i.e., average or hard endosperm) were planted in plots with similar soil and similar agronomic conditions and harvested in the same week. Both corn sources were dried at 35 °C or 120 °C. Results indicated that endosperm hardness did not influence the apparent ileal digestibility of starch or standardized ileal digestibility (SID) of amino acids (AA) in pigs; however, values for SID of most AA in corn dried at 120 °C were less than in corn dried at 35 °C. Hard endosperm corn also had greater apparent total tract digestibility of gross energy and total dietary fiber than corn with average endosperm, but drying temperature did not influence energy digestibility. Further research is needed to determine the optimum drying temperature and corn variety to maximize nutritional value in corn.

Methodology to Analyse Three-Dimensional Asymmetries in the Forces Applied to the Pedals in Cycling.

The asymmetries study between both legs of the forces applied to the pedals in cycling is important because they may affect the performance of the cyclist or prevent the occurrence of injuries. Studies focused on analysing asymmetries in forces tend to consider only the effective force, disregarding the three-dimensional nature of the force. Furthermore, these studies do not analyse the possible physical or neurological causes that may have led to the appearance of the asymmetries. This paper presents a methodology to carry out three-dimensional analysis of the asymmetries of the forces applied in both pedals and discriminate the possible sources of these asymmetries. Seven participants, amateurs and without pathologies, were analysed. Two commercial pedals were instrumented to measure the three components of the force applied to each pedal. The Normalized Symmetry Index (NSI) and the Cross Correlation Coefficient (CCC) were used for the asymmetries analysis. Results showed that both indexes need to be used in conjunction to analyse the causes of asymmetry in the pedal forces from a 3D perspective along the pedal cycle. The NSI is an index that makes it possible to evaluate asymmetry by considering only the value of the force applied by each leg at each instant. The CCC makes it possible to evaluate whether the temporal evolutions of the forces applied by each leg are similar. Preliminary results suggest that the proposed methodology is effective for analysing asymmetries in the forces in a pedalling cycle from a three-dimensional point of view. Forces in the sagittal plane showed a high level of symmetry. The lateral-medial force presented the highest level of asymmetry due to the difference in the magnitudes of the applied forces by both legs and the existing time shift between the two force patterns. The results of this work will allow for more complete and accurate three-dimensional dynamic analyses of the lower body during pedalling.

Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice.

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox-Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. METHODS: A multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. RESULTS: Eighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1-70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. CONCLUSION: This is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Design and Validation of a Device Attached to a Conventional Bicycle to Measure the Three-Dimensional Forces Applied to a Pedal.

Knowledge of the forces applied to the pedals during cycling is of great importance both from the point of view of improving sporting performance and medical analysis of injuries. The most common equipment for measuring pedal forces is usually limited to the study of forces in the sagittal plane. Equipment that measures three-dimensional forces tends to be bulky and to be incorporated into bicycles that are modified to accommodate it, which can cause the measurements taken to differ from those obtained in real pedalling conditions. This work presents a device for measuring the 3D forces applied to the pedal, attachable to a conventional bicycle and pedals, which does not alter the natural pedalling of cyclists. The equipment consists of four gauges located on the pedal axis and two on the crank, controlled by a microcontroller. Pedal forces measurements were made for six cyclists, with results similar to those shown in the literature. The correct estimation of the lateral-medial direction force is of great interest when evaluating a possible overload at the joints; it will also allow a comparison of the effectiveness index during pedalling, showing the role of this component in this index from a mechanical standpoint.

The Resurgence of Medical Ethics During the Coronavirus Disease (COVID)-19 Outbreak.

The unprecedented COVID-19 pandemic has risen a number of clinical situations where the principles of the medical act, the singularity of the patient-physician relationship and the need for revitalizing the medical vocation have all become at front line. Original articles, viewpoints, and perspectives addressing these aspects have appeared in major medical journals. Never before but perhaps with AIDS in the eighties, a disease awakened such feelings of commitment in medicine. Herein, we discuss some of these very sensitive issues for physicians that emerged during the past months of global COVID-19 crisis.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Use of intravenous brivaracetam in status epilepticus: A multicenter registry.

OBJECTIVE: The pharmacokinetics of brivaracetam (BRV), added to its effectiveness observed in animal models of status epilepticus (SE), makes this drug attractive for use in emergency situations. Our objective was to evaluate the use of intravenous BRV in a multicenter study. METHODS: A retrospective multicenter registry of SE cases treated with BRV was created. These patients were evaluated between January and December 2018 at seven hospitals in Spain. Demographic variables, SE characteristics, concomitant drugs, loading doses, and response to treatment were collected. RESULTS: Forty-three patients were registered. The mean age was 56 ± 23.1 years, 51.2% were male, 29 had previous epilepsy, 24 (55.8%) had prominent motor symptoms, and 19 had nonconvulsive symptoms. Regarding the etiology, 19 (44.2%) were considered acute symptomatic, 16 (17.2%) remote symptomatic, four (9.3%) progressive symptomatic, and four (9.3%) cryptogenic. Regarding concomitant antiepileptic drugs (AEDs), 17 had previously received levetiracetam (LEV). In 14 patients, BRV was used early (first or second AED). The median loading dose was 100 mg (range = 50-400), and the weight-adjusted dose was 1.8 mg/kg (range = 0.4-7.3). BRV was effective in 54% (n = 23), and a response was observed in <6 hours in 13 patients. We observed a tendency for it to be more effective when administered earlier (P = 0.09), but there were no differences regarding SE type and the concomitant use of LEV. In those with the fastest responses, we observed that both the total administered dose (300 mg vs 100 mg, P = 0.008) and the weight-adjusted dose (3.85 mg vs 1.43 mg, P = 0.006) were significantly higher. The receiver operating characteristic curve showed that the best cutoff point for a faster response was 1.82 mg/kg. SIGNIFICANCE: BRV is useful for the treatment of SE, even when patients are already being treated with LEV. The response rate seems higher when it is administered earlier and at higher doses (>1.82 mg/kg).

MONOZEB: Long-term observational study of eslicarbazepine acetate monotherapy.

AIM: The aim of the study was to evaluate the effectiveness and tolerability of eslicarbazepine acetate (ESL) when used as monotherapy for 1 year or more in routine clinical use in patients with focal seizures in epilepsy clinics in Spain. METHODS: This is a retrospective, observational, noninterventional study. Eligible patients were aged ≥18 years, had focal seizures, and started on ESL ≥1 year before database closure. Primary endpoint was the following: proportion seizure-free for ≥6 months at 1 and 2 years. Secondary endpoints included retention on ESL monotherapy at 1 and 2 years, seizure frequency change, seizure worsening, and side effects. Other analyses included seizure freedom from baseline to 1 and 2 years and outcomes in special populations. RESULTS: Four hundred thirty-five patients were included (127 on first-line monotherapy and 308 converting to ESL monotherapy): median daily dose was 800 mg at all time points; 63.2% were seizure-free at 1 year, 65.1% at 2 years, and 50.3% for the entire follow-up. Mean duration of ESL monotherapy was 66.7 months; retention was 88.0% at 1 year and 81.9% at 2 years. Mean reduction in seizure frequency was 75.5% at last visit. Over the entire follow-up, seizure worsening was seen in 22 patients (5.1%), side effects in 28.0%, considered severe in 1.8%, and leading to discontinuation in 5.7%. Dizziness, hyponatremia (sodium <135 mEq/l), and somnolence were the most frequent side effects. Outcomes in special populations (patients aged ≥65 years and those with psychiatric history or learning difficulty) were consistent with the overall population. CONCLUSIONS: Patients with focal seizures taking ESL monotherapy had excellent retention, high seizure-free rates, and good tolerability up to 2 years.

A procedure to estimate normal and friction contact parameters in the stance phase of the human gait.

A new approach to estimate normal and tangential contact parameters in the foot-ground contact during human gait was proposed. A correct estimation of the contact parameters would be very important in the resolution of predictive forward dynamic problems. The normal contact forces have been well estimated in the literature. But accurate estimation of tangential forces has not been reached yet. This work proposed a new procedure to accurately estimate friction forces. The approach has been based on the consideration of the modulus of the tangential force instead of its components. This modulus was introduced together with the modulus of the normal contact force and its two associated moments in an optimization algorithm to fit the contact forces provided by the model to the experimental data obtained with a force plate. An inverse dynamics problem was solved as a step previous to the optimization algorithm. The results showed that both the normal and tangential forces and the moments in the horizontal plane were in agreement with the experimental measurements. This work also analyzed the influence on the results of the friction law. The results obtained with the general friction law, which considered dry (static and dynamic) and viscous friction, were compared with results provided by simpler laws. The analysis of the components of the friction forces pointed out the importance of the Stribeck component in the resultant force instead of the viscous friction which played a minimal role. But for modelling the stick-slip transition, the implementation of a general friction law is necessary.

Analysis of Spatial and Temporal Step Parameters During Crutch-Assisted Gait as a Dual-Task: A Pilot Study.

The main objective was to analyze the changes in the spatial and temporal step parameters during a dual-task: walking with a forearm crutch to partially unload the body weight of the subject. The secondary objective was to determine the influence of the use of the crutch with the dominant or nondominant hand in the essential gait parameters. Seven healthy subjects performed gait without crutches (GWC) and unilateral assisted gait (UAG) with the crutch carried out by dominant hand (dominant crutch (DC)) and nondominant hand (nondominant crutch (NDC)). Gait was recorded using a Vicon System; the GCH System 2.0 and the GCH Control Software 1.0 controlled the loads. The variables were step length, step period, velocity, step width, and step angle. The Wilcoxon signed-rank test compared GWC and UAG while also analyzing the parameters measured for both legs with DC and NDC in general and in each subject. Wilcoxon test only found significant differences in 1 of the 15 general comparisons between both legs. In the analysis by subject, step length, step period, and velocity showed significant differences between GWC and UAG. These parameters obtained less differences in DC. The effect of a forearm crutch on UAG caused a reduction in step length and velocity, and an increase in step period. However, it did not entail changes in step angle and step width. UAG was more effective when the DC carried the crutch. The unloading of 10% body weight produced an assisted gait which closely matched GWC.

Influence of the load exerted over a forearm crutch in spatiotemporal step parameters during assisted gait: pilot study.

BACKGROUND: Assisted gait with forearm crutches is frequently performed during the recovery of musculoskeletal injuries of the lower limb. The amount of body weight applied to the crutch or crutches depends on the pathology and the treatment phase. The transition from assisted gait with two crutches to a single crutch is usually recommended when the subject is able to load the 50% of the body weight upon the affected member. An altered assisted gait will cause biomechanic alterations and, therefore, longer treatments and relapses. The aim of this study was to analyze the influence of 10, 25 and 50% of body weight applied to a forearm crutch during a unilateral assisted gait in the spatial and temporal step parameters to determine the load that produces alterations in gait biomechanics and the load that does not. METHODS: Eleven healthy subjects performed normal gait (NG) and assisted gait with a forearm crutch, in which the applied loads were: comfortable (C), 25 and 50% of their body weight. Vicon System was employed for gait recording. GCH System 2.0 and GCH Control Software 1.0 controlled the loads. The variables were: step length, step period, velocity, step width and step angle. Friedman test compared all the gait modalities: NG and the different loads. Wilcoxon signed-rank test analyzed ipsilateral and contralateral step parameters to the crutch globally and for each subject. RESULTS: Friedman test showed significant differences between NG, C, 25 and 50%, especially for step period and velocity. Wilcoxon test had significant differences only in 4 of the 20 general comparisons between ipsilateral and contralateral steps to the crutch. In the analysis by subjects, step length, step period and velocity showed 79/132, 110/132 and 58/66 significant differences, respectively. CONCLUSIONS: The increase in the load exerted over a forearm crutch produced an increase in the step period, accompanied by a reduction of step length and gait velocity. Step width and step angle were not modified. The unloading of 25 and 50% of body weight on a single crutch is incorrect from the biomechanical point of view. Two crutches should be employed when the body weight to unload exceeds 10%.

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.

Reliability and Validity Study of the Chamorro Assisted Gait Scale for People with Sprained Ankles, Walking with Forearm Crutches.

OBJECTIVE: The aim of this study was to design and validate a functional assessment scale for assisted gait with forearm crutches (Chamorro Assisted Gait Scale-CHAGS) and to assess its reliability in people with sprained ankles. DESIGN: Thirty subjects who suffered from sprained ankle (anterior talofibular ligament first and second degree) were included in the study. A modified Delphi technique was used to obtain the content validity. The selected items were: pelvic and scapular girdle dissociation(1), deviation of Center of Gravity(2), crutch inclination(3), steps rhythm(4), symmetry of step length(5), cross support(6), simultaneous support of foot and crutch(7), forearm off(8), facing forward(9) and fluency(10). Two raters twice visualized the gait of the sample subjects which were recorded. The criterion-related validity was determined by correlation between CHAGS and Coding of eight criteria of qualitative gait analysis (Viel Coding). Internal consistency and inter and intra-rater reliability were also tested. RESULTS: CHAGS obtained a high and negative correlation with Viel Coding. We obtained a good internal consistency and the intra-class correlation coefficients oscillated between 0.97 and 0.99, while the minimal detectable changes were acceptable. CONCLUSION: CHAGS scale is a valid and reliable tool for assessing assisted gait with crutches in people with sprained ankles to perform partial relief of lower limbs.

On the Use of Bone Remodelling Models to Estimate the Density Distribution of Bones. Uniqueness of the Solution.

Bone remodelling models are widely used in a phenomenological manner to estimate numerically the distribution of apparent density in bones from the loads they are daily subjected to. These simulations start from an arbitrary initial distribution, usually homogeneous, and the density changes locally until a bone remodelling equilibrium is achieved. The bone response to mechanical stimulus is traditionally formulated with a mathematical relation that considers the existence of a range of stimulus, called dead or lazy zone, for which no net bone mass change occurs. Implementing a relation like that leads to different solutions depending on the starting density. The non-uniqueness of the solution has been shown in this paper using two different bone remodelling models: one isotropic and another anisotropic. It has also been shown that the problem of non-uniqueness is only mitigated by removing the dead zone, but it is not completely solved unless the bone formation and bone resorption rates are limited to certain maximum values.

An unusual cause of respiratory failure in a colon cancer patient.

Permanent central venous catheters (CVC), such as Port-a-Cath®, Hickmann® or PICC®, are widely used in oncology patients for cancer treatment. Thrombosis is a frequent complication that should be ruled out, as it is associated with potentially severe infection and hemodynamic consequences. This is the case report of a male patient who was undergoing chemotherapy for colon cancer. The patient presented with an atrial mass secondary to a CVC-related organized thrombus located inside the atrial cavity. The mass was inducing a massive right-to-left intracardial shunt due to a persistent foramen ovale and signs of respiratory failure that required surgical intervention to remove the intracardial mass.

Long-term efficacy and safety of lacosamide monotherapy in the treatment of partial-onset seizures: A multicenter evaluation.

PURPOSE: The goal of this study is to report the efficacy and tolerability of lacosamide (LCM) monotherapy, as first-line and conversion regimens, in the treatment of patients with partial-onset seizures. METHODS: We retrospectively reviewed the charts of patients with focal epilepsy on LCM monotherapy from six centers in Spain. Efficacy and tolerability were evaluated in the overall group and in subgroups of patients who were naive to antiepileptic drug (AED) therapy (Group 1) and those who had previously been treated with AEDs (Group 2). RESULTS: Sixty-six patients were identified including 18 patients in Group 1 and 48 patients in Group 2. Patients were followed up for 0.5-54 months in monotherapy (mean 15.5 months). Forty-two (63.6%) patients remained seizure-free during all the follow-up. At 6 and 12 months, seizure-free rates were 77.6% and 72.3%, respectively. The drug was withdrawn in 10 (15%) patients (3 side effects, 6 lack of efficacy, 1 other reason). Fifteen (22.7%) patients reported mild to moderate side effects with the use of LCM. No differences were found between Groups 1 and 2 regarding efficacy outcomes or tolerability issues. CONCLUSIONS: In our series more than two-thirds of the patients remained seizure-free on LCM monotherapy. Side effects were generally mild and led to discontinuation in only 3/66 (4.5%) patients. Our experience suggests that LCM monotherapy, either as first-line or after conversion, may be a valuable option for patients with focal epilepsy.

Finite element analysis of the human mastication cycle.

The aim of this paper is to propose a biomechanical model that could serve as a tool to overcome some difficulties encountered in experimental studies of the mandible. One of these difficulties is the inaccessibility of the temporomandibular joint (TMJ) and the lateral pterygoid muscle. The focus of this model is to study the stresses in the joint and the influence of the lateral pterygoid muscle on the mandible movement. A finite element model of the mandible, including the TMJ, was built to simulate the process of unilateral mastication. Different activation patterns of the left and right pterygoid muscles were tried. The maximum stresses in the articular disc and in the whole mandible during a complete mastication cycle were reached during the instant of centric occlusion. The simulations show a great influence of the coordination of the right and left lateral pterygoid muscles on the movement of the jaw during mastication. An asynchronous activation of the lateral pterygoid muscles is needed to achieve a normal movement of the jaw during mastication.

[Edmund D. Pellegrino justice]. / La Justicia en Edmund D. Pellegrino.

Edmund D. Pellegrino has dedicated a significant amount of his time analyzing the virtue of justice in medicine, aware that it's misinterpretation could drive to an important load of suffering in vulnerable population, such as elderly or poor patients. The author also studies the impact of social changes as well as science and technology development in doctor-patient relationship, spinal cord of every justice-based health system.

La justicia en Edmund. D. Pellegrino / Edmund D. Pellegrino Justice

Edmundo D. Pellegrino dedica una significativa parte de su pensamiento a profundizar en el sentido de justicia en medicina como virtud, consciente de que una mala interpretación de ésta pude llevar a importante sufrimiento a una parte importante de la población, especialmente a los ancianos y personas sin recursos. El autor analiza el impacto que tiene los cambios sociales y el avance de la ciencia y tecnología en la relación médico-paciente, eje vertebrador de todo sistema sanitario justo

Edmund D. Pellegrino has dedicated a significant amount of his time analyzing the virtue of justice in medicine, aware that it´s misinterpretation could drive to an important load of suffering in vulnerable population, such as elderly or poor patients. The author also studies the impact of social changes as well as science and technology development in doctor-patient relationship, spinal cord of every justice-based health system