Protective effects of antioxidants on striatal dopamine release induced by organophosphorus pesticides.

Although the toxic effects of organophosphorus (OP) pesticides have been classically attributed to inhibition of the acetylcholinesterase, other neurotoxic mechanisms, as oxidative stress can also occur. Here we evaluated if antioxidants prevent the excessive dopamine release induced by OP pesticides in conscious and freely moving rats, using cerebral microdialysis technique. Intrastriatal infusion of paraoxon (5 mM), glufosinate (10 mM) or glyphosate (5 mM) significantly increased the dopamine release (1006 ± 106%, 991 ± 142%, and 1164 ± 128%, relative to baseline, respectively). To evaluate if these increased dopamine release could be related to oxidative stress, we pretreated animals with antioxidants glutathione (GSH, 400 or 800 µM), dithiothreitol (DTT, 5 or 10 µM), trolox (1 or 3 mM), and α-lipoic acid (ALA, 400 or 800 µM) before administration of OP pesticides. Intrastriatal administration of the antioxidants GSH, DTT, trolox, and ALA was highly effective in preventing the glyphosate and glufosinate-induced dopamine overflow. However, only GSH (800 µM) significantly decreased the effect of paraoxon on dopamine levels. The high toxicity of this pesticide and the low concentrations used could explain this lack of effect in our experimental conditions. The fact that ROS scavengers prevent the excessive dopamine release induced by OP pesticides, further supports the view that dopamine overflow can cause neuronal damage mediated, at least in part, by oxidative stress.

[Epidemiology and clinical features of malignant melanoma. Analysis of 274 cases]. / Epidemiología y características anatomoclínicas del melanoma maligno en un instituto oncológico.

BACKGROUND: Malignant melanoma (MM) is the most fatal cutaneous neoplasm. Its incidence is increasing progressively, which cannot be explained only by early diagnosis. Chilean population, due to the geography of the country, has a very varied solar exposure. AIM: To know the incidence of MM in a Chilean population, according to the level of sun exposure and to describe its clinical and histopathological characteristics. MATERIAL AND METHODS: Two hundred seventy-four surgeries for malignant melanoma with histological confirmation, carried out between 2016 and 2018 in an oncological institute were included. RESULTS: The annualized incidence of MM was 13.83 cases per 100,000 people over 15 years of age in the 2016-2018 period. The geographical distribution of the incidence did not have a clear relationship with sun exposure. The most frequent locations of the primary lesions were trunk, head/neck and lower limb. Sixty-one per cent of cases were invasive MM; lesion thickness and presence of ulceration were associated with a higher risk of sentinel node involvement. CONCLUSIONS: No association between the level of sun exposure and the incidence of MM was observed in this study.

COVID-19 fatality in Mexico's indigenous populations.

OBJECTIVE: The aim of the study was to explore the factors that could explain the differences in fatality rates among indigenous groups with COVID-19 diagnosis compared with the rest of the population in Mexico. STUDY DESIGN: We analyzed the public data of COVID-19 surveillance, of the Mexican Ministry of Health, to estimate COVID-19 fatality rates by ethnicity. METHODS: We explored associated factors using Cox proportional hazards models stratified by outpatient and hospital management at diagnosis; analysis was conducted in three scenarios: national level, states with 89% of the indigenous population, and South Pacific region. RESULTS: A total of 412,017 COVID-19 cases were included, with 1.1% of the indigenous population. The crude fatality rate per 1000 person-weeks was 64.8% higher among indigenous than among non-indigenous people (29.97 vs. 18.18, respectively), and it increased more than twice within outpatients (5.99 vs. 2.64, respectively). Cox analysis revealed that indigenous people who received outpatient management had higher fatality rate than non-indigenous outpatients, at the national level (hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.34-1.98), within the subgroup of 13 states (HR = 1.66; 95% CI = 1.33-2.07), and in the South Pacific region (HR = 2.35; 95% CI = 1.49-3.69). Factors associated with higher fatality rates among non-indigenous and indigenous outpatients were age, sex, and comorbidities. CONCLUSIONS: COVID-19 fatality is higher among indigenous populations, particularly within cases managed as outpatients.

[Diaphragmatic pacemaker as an alternative to mechanical ventilation in patients with cervical spinal injury]. / Marcapasos diafragmático como alternativa a la ventilación mecánica en el paciente con lesión medular cervical.

OBJECTIVE: To verify that the diaphragmatic pacemaker is a form of respiratory support that can be used to replace a volumetric respirator in cervical spinal injury patients with cervical spinal lesion and diaphragmatic paralysis by means of its comparison with the traditional volumetric respirator. DESIGN: Retrospective study of a prospective database and age-matched case-control study. SETTING: Intensive Care Unit and Intermediate Care Respiratory Unit, Paraplegics National Hospital, Toledo (Spain). PATIENTS: We collected data on all patients discharged from the Hospital with permanent respiratory support by volumetric respirator or diaphragmatic pacemaker during a follow-up period of 25 years. Personal interviews were conducted to evaluate health-related quality of life. Comparison and survival tests were used for statistical comparisons. INTERVENTIONS: Quality of life questionnaire. MAIN VARIABLES: The main variables collected were demographic data, hospital stay, mortality, family reintegration and health-related quality of life. RESULTS: We evaluated the clinical records of 101 patients, 37 in the pacemaker-group and 64 in the volumetric respirator-group. Our results show that ICU admission duration and hospitalization as well as family reintegration, without significant differences, with a tendency to greater survival in pacemaker patients (18.18 versus 9.67 years by the Kaplan-Meier method, p<0.001). However, this difference becomes non-significant (p=0.06) after adjustment of the groups by age. Furthermore, better quality of life was found in these same patients with pacemakers in terms of security, communication, sociability, comfort and mobility in the patients. CONCLUSIONS: Diaphragmatic pacemaker ventilation is an effective alternative to mechanical ventilation with similar efficacy that improve quality of life in patients with severe respiratory failure due to cervical spinal cord injury.

Development and large volume production of extremely high current density YBa2Cu3O7 superconducting wires for fusion.

The fusion power density produced in a tokamak is proportional to its magnetic field strength to the fourth power. Second-generation high temperature superconductor (2G HTS) wires demonstrate remarkable engineering current density (averaged over the full wire), JE, at very high magnetic fields, driving progress in fusion and other applications. The key challenge for HTS wires has been to offer an acceptable combination of high and consistent superconducting performance in high magnetic fields, high volume supply, and low price. Here we report a very high and reproducible JE in practical HTS wires based on a simple YBa2Cu3O7 (YBCO) superconductor formulation with Y2O3 nanoparticles, which have been delivered in just nine months to a commercial fusion customer in the largest-volume order the HTS industry has seen to date. We demonstrate a novel YBCO superconductor formulation without the c-axis correlated nano-columnar defects that are widely believed to be prerequisite for high in-field performance. The simplicity of this new formulation allows robust and scalable manufacturing, providing, for the first time, large volumes of consistently high performance wire, and the economies of scale necessary to lower HTS wire prices to a level acceptable for fusion and ultimately for the widespread commercial adoption of HTS.

Economic evaluation of public-private mix for tuberculosis care and control, India. Part II. Cost and cost-effectiveness.

SETTING: Bangalore City, India. OBJECTIVES: To assess the cost and cost-effectiveness of public-private mix (PPM) for tuberculosis (TB) care and control when implemented on a large scale. DESIGN: DOTS implementation under the Revised National TB Control Programme (RNTCP) began in 1999, PPM was introduced in mid-2001 and a second phase of intensified PPM began in 2003. Data on the costs and effects of TB treatment from 1999 to 2005 were collected and used to compare the two distinct phases of PPM with a scenario of no PPM. Costs were assessed in 2005 $US for public and private providers, patients and patient attendants. Sources of data included expenditure records, medical records, interviews with staff and patient surveys. Effectiveness was measured as the number of cases successfully treated. RESULTS: When PPM was implemented, total provider costs increased in proportion to the number of successfully treated TB cases. The average cost per patient treated from the provider perspective when PPM was implemented was stable, at US$69, in the intensified phase compared with US$71 pre-PPM. PPM resulted in the shift of an estimated 7200 patients from non-DOTS to DOTS treatment over 5 years. PPM implementation substantially reduced costs to patients, such that the average societal cost per patient successfully treated fell from US$154 to US$132 in the 4 years following the initiation of PPM. CONCLUSION: Implementation of PPM on a large scale in an urban setting can be cost-effective, and considerably reduces the financial burden of TB for patients.

Automatic pedicle screw planning using atlas-based registration of anatomy and reference trajectories.

An algorithm for automatic spinal pedicle screw planning is reported and evaluated in simulation and first clinical studies. A statistical atlas of the lumbar spine (N = 40 members) was constructed for active shape model (ASM) registration of target vertebrae to an unsegmented patient CT. The atlas was augmented to include 'reference' trajectories through the pedicles as defined by a spinal neurosurgeon. Following ASM registration, the trajectories are transformed to the patient CT and accumulated to define a patient-specific screw trajectory, diameter, and length. The algorithm was evaluated in leave-one-out analysis (N = 40 members) and for the first time in a clinical study (N = 5 patients undergoing cone-beam CT (CBCT) guided spine surgery), and in simulated low-dose CBCT images. ASM registration achieved (2.0 ± 0.5) mm root-mean-square-error (RMSE) in surface registration in 96% of cases, with outliers owing to limitations in CT image quality (high noise/slice thickness). Trajectory centerlines were conformant to the pedicle in 95% of cases. For all non-breaching trajectories, automatically defined screw diameter and length were similarly conformant to the pedicle and vertebral body (98.7%, Grade A/B). The algorithm performed similarly in CBCT clinical studies (93% centerline and screw conformance) and was consistent at the lowest dose levels tested. Average runtime in planning five-level (lumbar) bilateral screws (ten trajectories) was (312.1 ± 104.0) s. The runtime per level for ASM registration was (41.2 ± 39.9) s, and the runtime per trajectory was (4.1 ± 0.8) s, suggesting a runtime of ~(45.3 ± 39.9) s with a more fully parallelized implementation. The algorithm demonstrated accurate, automatic definition of pedicle screw trajectories, diameter, and length in CT images of the spine without segmentation. The studies support translation to clinical studies in free-hand or robot-assisted spine surgery, quality assurance, and data analytics in which fast trajectory definition is a benefit to workflow.

Current distribution across type II superconducting films: a new vortex-free critical state.

The current distribution across the thickness of a current-carrying rectangular film in the Meissner state was established long ago by the London brothers. The distribution across the width is more complicated but was later shown to be highly non-uniform, diverging at the edges. Accordingly, the standard view for type II superconductors is that vortices enter at the edges and, with increasing current, are driven inwards until they self-annihilate at the centre, causing dissipation. This condition is presumed to define the critical current. However we have shown that, under self-field (no external field), the transport critical current is a London surface current where the surface current density equals the critical field divided by λ, across the entire width. The critical current distribution must therefore be uniform. Here we report studies of the current and field distribution across commercial YBa2Cu3 O7 conductors and confirm the accepted non-uniform distribution at low current but demonstrate a radical crossover to a uniform distribution at critical current. This crossover ends discontinuously at a singularity and calculations quantitatively confirm these results in detail. The onset of self-field dissipation is, unexpectedly, thermodynamic in character and the implied vortex-free critical state seems to require new physics.

The onset of dissipation in high-temperature superconductors: magnetic hysteresis and field dependence.

Recently, we showed that the self-field transport critical current, Ic(sf), of a superconducting wire can be defined in a more fundamental way than the conventional (and arbitrary) electric field criterion, Ec = 1 µV/cm. We defined Ic(sf) as the threshold current, Ic,B, at which the perpendicular component of the local magnetic flux density, B⊥, measured at any point on the surface of a high-temperature superconducting tape abruptly crosses over from a non-linear to a linear dependence with increasing transport current. This effect results from the current distribution across the tape width progressively transitioning from non-uniform to uniform. The completion of this progressive transition was found to be singular. It coincides with the first discernible onset of dissipation and immediately precedes the formation of a measureable electric field. Here, we show that the same Ic,B definition of critical currents applies in the presence of an external applied magnetic field, Ba. In all experimental data presented here Ic,B is found to be significantly (10-30%) lower than Ic,E determined by the common electric field criterion of Ec = 1 µV/cm, and Ec to be up to 50 times lower at Ic,B than at Ic,E.

Epidemiología y características anatomoclínicas del melanoma maligno en un instituto oncológico / Epidemiology and clinical features of malignant melanoma. Analysis of 274 cases

BACKGROUND: Malignant melanoma (MM) is the most fatal cutaneous neoplasm. Its incidence is increasing progressively, which cannot be explained only by early diagnosis. Chilean population, due to the geography of the country, has a very varied solar exposure. AIM: To know the incidence of MM in a Chilean population, according to the level of sun exposure and to describe its clinical and histopathological characteristics. MATERIAL AND METHODS: Two hundred seventy-four surgeries for malignant melanoma with histological confirmation, carried out between 2016 and 2018 in an oncological institute were included. RESULTS: The annualized incidence of MM was 13.83 cases per 100,000 people over 15 years of age in the 2016-2018 period. The geographical distribution of the incidence did not have a clear relationship with sun exposure. The most frequent locations of the primary lesions were trunk, head/neck and lower limb. Sixty-one per cent of cases were invasive MM; lesion thickness and presence of ulceration were associated with a higher risk of sentinel node involvement. CONCLUSIONS: No association between the level of sun exposure and the incidence of MM was observed in this study.

Market assessment of tuberculosis diagnostics in China in 2012.

OBJECTIVE: To assess the 2012 served available market for tuberculosis (TB) diagnostics in China in the sector served by the China Centre for Disease Control and Prevention (CDC) and the hospital sector in China, including both designated TB hospitals and general hospitals. DESIGN: Test volumes and unit costs were assessed for tuberculin skin tests, interferon-gamma release assays (IGRAs), smear microscopy, serology, cultures, speciation tests, nucleic-acid amplification tests (NAATs), drug susceptibility tests and adenosine-deaminase tests (ADA). Data were obtained from electronic databases (CDC sector) and through surveys (hospital sector), and were estimated for the two sectors and for the country as a whole. Test costs were estimated by staff at China CDC, and using published literature. RESULTS: In 2012, the China CDC and hospital sectors performed a total of 44 million TB diagnostic tests at an overall value of US$294 million. Tests used by the CDC sector were smear microscopy, solid and liquid culture and DST, while the hospital sector also used IGRAs, NAATs, ADA and serology. The hospital sector accounted for 76% of the overall test volume and 94% of the market value. CONCLUSION: China has a very large TB diagnostic market that encompasses a wide range of diagnostic tests, with the majority being performed in Chinese hospitals.

Market assessment of tuberculosis diagnostics in India in 2013.

BACKGROUND: India represents a significant potential market for new tests. We assessed India's market for tuberculosis (TB) diagnostics in 2013. METHODS: Test volumes and unit costs were assessed for tuberculin tests, interferon-gamma release assays, sputum smear microscopy, serology, culture, speciation testing, nucleic-acid amplification tests (i.e., in-house polymerase chain reaction, Xpert(®) MTB/RIF, line-probe assays) and drug susceptibility testing. Data from the public sector were collected from the Revised National TB Control Programme reports. Private sector data were collected through a survey of private laboratories and practitioners. Data were also collected from manufacturers. RESULTS: In 2013, India's public sector performed 19.2 million tests, with a market value of US$22.9 million. The private sector performed 13.6 million tests, with a market value of US$60.4 million when prices charged to the patient were applied. The overall market was US$70.8 million when unit costs from the ingredient approach were used for the 32.8 million TB tests performed in the entire country. Smear microscopy was the most common test performed, accounting for 25% of the overall market value. CONCLUSION: India's estimated market value for TB diagnostics in 2013 was US$70.8 million. These data should be of relevance to test developers, donors and implementers.

Bryophytes in fragments of Terra Firme forest on the great curve of the Xingu River, Pará state, Brazil.

Microclimatic conditions of tropical forest favour the high richness of bryophytes, which by being sensitive to environmental changes, are important indicators of habitat conditions. The aim of this study was to determine the richness and species composition of the bryophyte flora in fragments of terra firme forest on the great curve of the Xingu River, Pará state, Brazil. The collections were made in August and September 2012 in 14 fragments, in which were installed two plots per fragment, one at the edge and one inside, measuring 10 × 10 m each. The results showed 77 species in 45 genera and 18 families. Lejeunea setiloba Spruce and Marchesinia brachiata (Sw.) Schiffn. are new records for Pará state. The richness families in this study were the ones typically found in tropical forest surveys. A high richness of rare species in comparison to common ones, a pattern usually observed for plants in tropical forests was not reported in this study, probably due to historical fragmentation and disturbance in the area. The richness and species composition were determined mainly by the physiognomic characteristics of the studied forest fragments.

Effect of prophylactic phenobarbital on intraventricular hemorrhage in high-risk infants.

Forty-two premature infants less than 24 hours of age, with normal admission echoencephalograms, were randomly assigned to control or phenobarbital treatment groups. Infants in the treated group received two loading doses of 10 mg/kg of phenobarbital 12 hours apart, followed by a maintenance dose of 2.5 mg/kg every 12 hours for 6 days. Serial echoencephalograms were obtained in both groups. The groups were comparable with regard to birth weight, gestational age, and potential risk factors for subependymal-intraventricular hemorrhage. Ten infants (48%) in each group developed hemorrhage. The hemorrhages in the phenobarbital-treated group were significantly less severe than those in the control group. The phenobarbital-treated infants who bled, however, were also significantly larger and more mature than control infants who bled. The results of this study indicate no effect of phenobarbital on the incidence of subependymal-intraventricular hemorrhage, but a possible beneficial effect on the severity of hemorrhage.

A role for chloride in the suppressive effect of acetylcholine on afferent vestibular activity.

Afferents of the frog semicircular canal (SCC) respond to acetylcholine (ACh) application (0.3-1.0 mM) with a facilitation of their activity while frog saccular afferents respond with suppression (Guth et al., 1994). All recordings are of resting (i.e., non-stimulated) multiunit activity as previously reported (Guth et al., 1994). Substitution of 80% of external chloride (Cl-) by large, poorly permeant anions of different structures (isethionate, methanesulfonate, methylsulfate, and gluconate) reduced the suppressive effect of ACh in the frog saccular afferents. This substitution did not affect the facilitatory response of SCC afferents to ACh. Chloride channel blockers were also used to test further whether Cl- is involved in the ACh suppressive effect. These included: niflumic and flufenamic acids, picrotoxin, 5-nitro-2-(-3-phenylpropylamino)benzoic acid (NPPB), and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). As with the Cl- substitutions, all of these agents reduced the suppressive response to ACh in the saccule, but not the facilitatory response seen in the SCC. The suppressive effect of ACh on saccular afferents is considered to be due to activation of a nicotinic-like receptor (Guth et al., 1994; Guth and Norris, 1996). Taking into account the effects of both Cl- substitutions and Cl- channel blockers, we conclude that changes in Cl- availability influence the suppressive effect of ACh and that therefore Cl- may be involved in this effect.

A role for chloride in the hyperpolarizing effect of acetylcholine in isolated frog vestibular hair cells.

Acetylcholine (ACh) is the dominant transmitter released from inner ear efferent neurons. In frog vestibular organs, these efferent neurons synapse exclusively with type II hair cells. Hair cells isolated from the frog saccule hyperpolarize following the application of 50 microM ACh, thereby demonstrating the presence of an ACh receptor. A role for Cl(-) in the response of hair cell-bearing organs to efferent nerve activation or ACh application was suggested some years ago. Perfusion with solutions in which most of the Cl(-) was replaced by large impermeant anions decreased the cholinergic inhibition of afferent firing in the cat and turtle cochleas, and frog semicircular canal. Our previous work in the intact organ demonstrated that substitution of large impermeant anions for Cl(-) or use of Cl(-) channel blockers reduced the effect of ACh on saccular afferent firing. Using the perforated-patch clamping technique, replacement of Cl(-) by methanesulfonate, iodide, nitrate, or thiocyanate attenuated the hyperpolarizing response to ACh in hair cells isolated from the frog saccule. The chloride channel blockers picrotoxin and 4,4'-dinitrostilbene-2,2'-disulfonic acid were also tested and found to inhibit the ACh response. Thus, the present work demonstrates that the effects of Cl(-) substitutions or Cl(-) channel blockers on the ACh response in the intact saccule can be explained completely by effects on the hair cell. Evidence is also presented for the presence of the messenger RNA for a calcium-dependent chloride channel in all hair cells but especially saccular hair cells. This channel may be involved in the response to ACh. The precise role for chloride in this response, whether as a distinct ion current, as a transported ion, or as a permissive ion for other components, is discussed.

Studies of urine-associated acetaldehyde as a marker for alcohol intake in mice.

A study was undertaken in 16 male C57BL mice to evaluate the effect of ethanol intake via the drinking water (10% v/v) on urinary-associated acetaldehyde. Eight received ethanol and 8 served as controls. Urinary-associated acetaldehyde (UAA) was measured using a fluorigenic high performance chromatographic assay. Ethanol consumption did not impair growth over the two weeks of the experiment. Following administration of ethanol, UAA increased and remained significantly elevated over levels seen in controls until ethanol administration ceased (11.3 +/- 3.6 SEM microM for ethanol-consuming mice vs. 0.69 +/- 0.33 microM for controls). Ethanol in the urine was found to interfere with the assay for acetaldehyde. However, following cessation of ethanol, acetaldehyde in urine was found to be significantly elevated in urine at 24 hours, after ethanol levels were no longer detectable. In conclusion, measurement of urinary-associated acetaldehyde discriminates ethanol-consuming from nonconsuming mice during ethanol ingestion as well as 24 hours following cessation of ethanol when ethanol levels are no longer detectable in urine. Thus measurement of urinary acetaldehyde may be a useful marker for monitoring ethanol intake.

Population dynamics and effects of Oebalus ornatus (Hemiptera: Pentatomidae) on rice yield and quality in southwestern Colombia.

Field experiments were conducted from 1989 to 1992 to determine the effects of Oebalus ornatus (Sailer) on Cica 8 rice, Oryza sativa L., yield and to study the population dynamics of the insect. The effect of O. ornatus was measured for seven population levels (0, 2, 3, 4, 8, 12, and 24 sexed pairs per 20 panicles) at three stages of grain development (flowering, milk, and soft dough stage). Insect feeding during the flowering and milk stages of grain development caused more damage than feeding during the soft dough stage. The action threshold was calculated to be 14 O. ornatus adults per square meter for the flowering and milk stages and 67 for the soft dough stage of grain maturity. Population densities that would reduce rice yield in southwestern Colombia were not observed during the 3 yr of the study.