Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss.

The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.

Immunoglobulins in systemic sclerosis management. A large multicenter experience.

OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

A motor learning-based postural intervention with a robotic trunk support trainer to improve functional sitting in spinal cord injury: case report.

STUDY DESIGN: Single-subject-research-design. OBJECTIVES: To improve seated postural control in a participant with spinal cord injury (SCI) with a robotic Trunk-Support-Trainer (TruST). SETTING: Laboratory. METHODS: TruST delivered "assist-as-needed" forces on the participant's torso during a motor learning-and-control-based intervention (TruST-intervention). TruST-assistive forces were progressed and matched to the participant's postural trunk control gains across six intervention sessions. The T-shirt test was used to capture functional improvements while dressing the upper body. Kinematics were used to compute upper body excursions (cm) and velocity (cm2), and sitting workspace area (cm2). Functional trunk dynamometry was used to examine muscle force (Kg). Surface electromyography (sEMG) was applied to measure trunk muscle activity. The Borg Rating of Perceived Exertion (RPE) was used to monitor physical exertion during TruST-intervention. A two-standard-deviation bandwidth method was adopted for data interpretation. RESULTS: After TruST-intervention, the participant halved the time needed to don and doff a T-shirt, increased muscle force of trunk muscles (mean = 3 kg), acquired a steadier postural sitting control without vision (mean excursion baseline: 76.0 ± 2 SD = 5.25 cm and post-intervention: 44.1 cm; and mean velocity baseline: 3.0 ± 2 SD = 0.2 cm/s and post-intervention: 1.8 cm/s), and expanded his sitting workspace area (mean baseline: 36.7 ± 2 SD = 36.6 cm2 and post-intervention: 419.2 cm2). The participant increased his tolerance to counteract greater TruST-force perturbations in lateral and posterior directions. Furthermore, abdominal muscle activity substantially augmented after completion of TruST-intervention across all perturbation directions. CONCLUSIONS: Our data indicate a potential effectiveness of TruST-intervention to promote functional sitting in SCI.

Feasibility and tolerance of a robotic postural training to improve standing in a person with ambulatory spinal cord injury.

An ambulatory elder with SCI, AIS C, balance deficits, and right ankle-foot-orthosis participated. RobUST-intervention comprised six 90 min-sessions of postural tasks with pelvic assistance and trunk perturbations. We collected three baselines and two 1 week post-training assessments-after the first four sessions (PT1) and after the last two sessions (PT2). We measured Berg Balance Scale (BBS), four-stage balance test (4SBT)-including a 30 s-window with and without vision-standing workspace area, and reactive balance (measured as body weight%). Kinematics, center-of-pressure (COP), and electromyography (EMG) were analyzed to compute root-mean-square-COP (RMS-COP), the margin of stability (MoS), ankle range of motion, and integrated EMG (iEMG) normalized to baseline. The Borg Rating of Perceived Exertion (BRPE), and change in the Mean Arterial Pressure (MAP) and heart rate (HR) compared with baseline were collected to address training tolerance. A 2SD-bandwidth method was selected for data interpretation. The maximum BBS was achieved (1-point improvement). In the 4SBT, the participant completed 30 s (baseline = 20 s) with reduced balance variability during semi-tandem position without vision (RMS-COP baseline = 50.32 ± 2 SD = 19.64 mm; PT1 = 21.29 mm; PT2 = 19.34 mm). A trend toward increase was found in workspace area (baseline = 996 ± 359 cm2; PT1 = 1539 cm2; PT2 = 1138 cm2). The participant tolerated higher perturbation intensities (baseline mean = 25%body weight, PT2 mean = 44% body weight), and on average improved his MoS (3 cm), ankle range of motion (4°), and gluteus medius activity (iEMG = 10). RobuST-intervention was moderate-sort of hard (BRPE = 3-4). A substantial reduction in MAP (9%) and HR (30%) were observed. In conclusion, RobUST-intervention might be effective in ambulatory SCI.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

[Estimating the number of COVID-19 cases using a web-based tool: Results from the first week of the 'Covid-19 Trends' project in the Basque Country]. / Estimando el número de casos de COVID-19 mediante una herramienta web: resultados de la primera semana del proyecto «Covid-19 Trends¼ en Euskadi.

OBJECTIVE: In the Basque Country, two cases of COVID-19 were diagnosed on February 28 2020. On March 14, the Spanish Government established a state of alarm. Only cases confirmed by molecular biology (reverse-transcriptase polymerase chain reaction [RT-PCR]) were known. We launched a web-based surveillance tool to estimate the number of symptomatic cases of COVID-19 to contribute to Public Health decision-making. MATERIAL AND METHODS: We implemented an anonymous web questionnaire and disseminated it through online social media social. We collected epidemiological information about «time¼ (date of onset of symptoms), «place¼ (zip code), and «person¼ (gender, age). We compared cases detected by RT-PCR with the estimated cases, according to the case definition of the Ministry of Health. We calculated the questionnaire response rate and the cumulative incidence at 14days. RESULTS: Between March 19 and 26, 128,009 people answered the questionnaire (5.5% of the Basque population). Of these, 26,375 met the case definition (symptom prevalence of 21.4%). The estimated cases were almost six times more than COVID-19 positive RT-PCR. The estimated 14-day cumulative incidence was 578.3 per 100,000 population compared to RT-PCR positive cases, which was 139.6 per 100,000 population. CONCLUSIONS: This tool was useful in estimating the minimum number of symptomatic cases in the Basque Country, which could support Public Health actions.

Model reduction methodology for computational simulations of endovascular repair.

Endovascular aneurysm repair (EVAR) is a current alternative treatment for thoracic and abdominal aortic aneurysms, but is still sometimes compromised by possible complications such as device migration or endoleaks. In order to assist clinicians in preventing these complications, finite element analysis (FEA) is a promising tool. However, the strong material and geometrical nonlinearities added to the complex multiple contacts result in costly finite-element models. To reduce this computational cost, we establish here an alternative and systematic methodology to simplify the computational simulations of stent-grafts (SG) based on FEA. The model reduction methodology relies on equivalent shell models with appropriate geometrical and mechanical parameters. It simplifies significantly the contact interactions but still shows very good agreement with a complete reference finite-element model. Finally, the computational time for EVAR simulations is reduced of a factor 6-10. An application is shown for the deployment of a SG during thoracic endovascular repair, showing that the developed methodology is both effective and accurate to determine the final position of the deployed SG inside the aneurysm.

IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

Differences in sexual desire between women with clinical versus biochemical signs of hyperandrogenism in polycystic ovarian syndrome.

The role androgens play in female sexual desire remains unclear. We investigated whether androgen sensitivity or elevated androgen levels contributed to sexual desire using a motivational model of sexual desire. Eighty-five women diagnosed with polycystic ovary syndrome (PCOS) were categorized depending on whether they exhibited clinical symptoms of androgen sensitivity or high biochemical androgen levels. Additionally, instead of looking at desire as a uniform construct, we divided desire based on the reasons why women experienced desire, thus distinguishing desire to have sex for relational purposes from the desire to have sex for mating selection or physical pleasure. Findings confirmed that clinical signs suggesting sensitivity to androgen levels, but not biological levels of androgens per se predicted levels of sexual desire. Moreover, in agreement with our hypothesis, we found support for a relationship between androgen sensitivity and some, but not other aspects of sexual desire. Cues that are most closely related to mating selection were significantly associated with androgen sensitivity, but not cues associated with desiring sex to feel emotionally close or create a love bonding with a partner. This study presents a new way to investigate desire and shows some preliminary findings on the importance to consider androgen sensitivity when investigating the relationship between sexual desire and hormones.

Levobupivacaine vs. racemic bupivacaine in peribulbar anaesthesia: a randomized double blind study in ophthalmic surgery.

AIMS: The Authors examine the employement of a new anaesthetic agent, levobupivacaine 0.50% (S - enantiomer of racemic mixture of bupivacaine), for peribulbar anaesthesia in a randomized double blind study vs. racemic bupivacaine 0.50% alone or in association with hyaluronidase 10 IU x ml(-1). MATERIALS AND METHODS: 120 patients were divided into four groups of 30 each: group L (levobupivacaine 0.50%), group B (racemic bupivacaine 0.50%), group LH (levobupivacaine-hyaluronidase 10 IU x ml(-1)), group BH (racemic bupivacaine-hyaluronidase 10 IU x ml(-1)). RESULTS: The onset-time (14 +/- 3.2 min vs. 13 +/- 4.8 min) and the duration of anaesthesia (195 +/- 34.2 vs. 204 +/- 37.6) were similar. The ocular akinesia was evaluated with an 8 point system: it was considered sufficient for surgery with values of less than 5 points. The association with hyaluronidase increased the spread of local anaesthetics (76.6% of group LH, 73.3% of group BH) with local anaesthetics alone (60% of group L, 56.6% of group B). Moderate hypotension (<30% baseline) was reported in 3 patients (10%) of group L, 2 (6.6%) of group B, 1 (3.3%) of group LH and 2 (6.6%) of group BH. Statistical analysis (Student-Newman-Keuls test) was significant between group L vs. BH, B vs. BH and LH vs. BH as regards onset-time of anaesthesia; between group B vs. LH, B vs. BH and L vs. LH for the duration of anaesthesia. Chi square test for the general akinesia score showed significant results in group L vs. LH (p=0.043) and B vs. LH 8P =0.018); as regards the score 0, test reported significant values between groups B vs. LH (p=0.004) and B vs. BH (p=0.017). CONCLUSIONS: In conclusion levobupivacaine, a longlasting local anaesthetic with limited cardio and neurotoxicity, might be useful for vitreoretinal surgery in elderly patients, compared with general anaesthesia.

Connections of the superior paraolivary nucleus of the rat: projections to the inferior colliculus.

GABAergic neurotransmission contributes to shaping the response properties of inferior colliculus (IC) neurons. In rodents, the superior paraolivary nucleus (SPON) is a prominent and well-defined cell group of the superior olivary complex that sends significant but often neglected GABAergic projections to the IC. To investigate the trajectory, distribution and morphology of these projections, we injected the neuroanatomical tracer biotinylated dextran amine into the SPON of albino rats. Our results demonstrate that: (1) the SPON innervates densely all three subdivisions of the ipsilateral IC: central nucleus (CNIC), dorsal cortex (DCIC) and external cortex (ECIC). The SPON also sends a sparse projection to the contralateral DCIC via the commissure of the IC. (2) SPON axons are relatively thick (diameter >1.2 microm), ascend to the midbrain tectum in the medial aspect of the lateral lemniscus, and, for the most part, do not innervate the nuclei of the lateral lemniscus. (3) SPON fibers ramify profusely within the IC and bear abundant en passant and terminal boutons. (4) The axons of neurons in discrete regions of the SPON form two laminar terminal plexuses in the ipsilateral IC: a medial plexus that spans the CNIC and DCIC parallel to the known fibrodendritic laminae of the CNIC, and a lateral plexus located in the ECIC and oriented more or less parallel to the surface of the IC. (5) The projection from SPON to the ipsilateral IC is topographic: medial SPON neurons innervate the ventromedial region of the CNIC and DCIC and the ventrolateral region of the ECIC, whereas more laterally situated SPON neurons innervate more dorsolateral regions of the CNIC and DCIC and more dorsomedial regions of the ECIC. Thus, SPON fibers follow a pattern of distribution within the IC similar to that previously reported for intracollicular and corticocollicular projections.

Cochlear ablation in adult ferrets results in changes in insulin-like growth factor-1 and synaptophysin immunostaining in the cochlear nucleus.

Afferent activity modulates synaptic plasticity as well as the levels of activity-dependent molecules such as growth factors. Disruption of this activity due to deafferentation has been shown to result in an altered trophic support and consequently in changes in neuronal excitability and synaptic transmission. In the present study, to test whether lack of cochlear integrity results in changes in insulin-growth factor-1 (IGF-1) and synaptophysin immunostaining in the cochlear nucleus, the first relay structure in the auditory pathway, unilateral cochlear ablations were performed in adult ferrets. Changes in IGF-1 and synaptophysin immunostaining were assessed in the anteroventral (AVCN), posteroventral (PVCN) and dorsal cochlear nucleus (DCN) at 1, 20 and 90 days after deafferentation. An increase in IGF-1 immunostaining within AVCN, PVCN and DCN was observed ipsilaterally at all survival times after cochlear ablation when compared with the contralateral side and unoperated animals. This increase was accompanied by a significant ipsilateral increase in the mean gray level of synaptophysin immunostaining as well as a decrease in the area of synaptophysin immunostaining at 1 and 20 days after the ablation in AVCN, PVCN and DCN compared with the contralateral side and control animals. These changes in synaptophysin immunostaining were no longer present 90 days after cochlear ablation. The present results provide evidence of a persistent upregulation in IGF-1 and a transitory upregulation in synaptophysin levels in the cochlear nucleus that may reflect neuroprotective mechanisms following the loss of trophic support from spiral ganglion neurons.

Prevalence and potential risk factors for amitraz resistance in Boophilus microplus ticks in cattle farms in the State of Yucatan, Mexico.

Southern cattle tick, Boophilus microplus, control in the Mexican tropics is based on the application by spray, dip or pour-on of acaricides. In Mexico the first report of ticks resistant to amitraz was reported in 2002. Amitraz resistance affecting the cattle industry of Yucatan State, Mexico, has not been investigated. A cross-sectional study was carried out in order to investigate the possible association between management risk factors and the prevalence of B. microplus ticks resistant to amitraz in Yucatan, Mexico. Ninety-eight cattle farms were randomly selected and a sample of 20-30 engorged B. microplus females was collected from at least 10 cattle from each farm. Collected ticks were taken to the laboratory where the larval progeny were obtained. The modified larval immersion test was used to detect ticks resistant to amitraz. A discriminating dose of 0.0002% amitraz was used. A questionnaire was applied on each collaborating farm. For the statistical analysis a 2x2 contingency table was used to identify potential risk factors. The prevalence of farms with B. microplus resistant to amitraz was 19.40%. However, even though tick resistance to amitraz is a present problem there was no evidence that it was associated with the risk factors analyzed in this survey.

Prevalence and potential risk factors for organophosphate and pyrethroid resistance in Boophilus microplus ticks on cattle ranches from the State of Yucatan, Mexico.

A cross-sectional study was carried out in order to investigate the association between management risk factors and the prevalence of organophosphate (OP) and synthetic pyrethroid (SP) resistance in Boophilus microplus ticks in Yucatan State, Mexico. Ninety-eight cattle ranches were randomly selected and a sample of 20-30 engorged female B. microplus ticks was collected at each. The modified larvae packet test was used to detect OP and SP tick resistance. A questionnaire was administered on each ranch. For risk factors, four reference types of response were used: Tuxpan (resistant to coumaphos, chlorfenvinphos and diazinon), Parkhurst (resistant to flumethrin, deltamethrin and cypermethrin), Lamington (resistant to flumethrin in absence of deltamethrin and cypermethrin) and Marmor (resistant to flumethrin and cypermethrin in absence of flumethrin). A primary screening was performed using 2 x 2 contingency tables of exposure variables. All variables with p < or = 0.20 were analyzed by a logistic regression. The prevalence of B. microplus resistance to OP and SP groups were 83.70% and 66.32%, respectively. The prevalence for a single chemical compound was: diazinon (80.60%), coumaphos (45.90%), chlorfenvinphos (35.70%), flumethrin (63.28%), deltamethrin (61.22%), and cypermethrin (59.18%). The prevalence type of response was: Tuxpan (34.16%), Parkhurst (58.16%), Lamington (4.08%), and Marmor (4.08%). The use of a different tick control program was the risk management factor associated with the Parkhurst type of response. It is concluded that the prevalence of cattle ranches with B. microplus resistant to OPs and SPs in Yucatan, Mexico, is a current problem, and a treatment interval of > or =6 times/year and use of a tick control program (macrocyclic lactones and pasture burn) different from standard recommended programs are risk factors associated with the Parkhurst type of response.