Microbial pesticides - challenges and future perspectives for testing and safety assessment with respect to human health.

Plant protection measures are necessary to prevent pests and diseases from attacking and destroying crop plants and to meet consumer demands for agricultural produce. In the last decades the use of chemical pesticides has largely increased. Farmers are looking for alternatives. Biopesticides should be considered a sustainable solution. They may be less toxic than chemical pesticides, be very specific to the target pest, decompose quickly, and be less likely to cause resistance. On the other hand, lower efficacy and higher costs are two disadvantages of many biopesticides. Biopesticides include macroorganisms, natural compounds and microorganisms. Microbial pesticides are the most widely used and studied class of biopesticides. The greatest difference between microbial and chemical pesticides is the ability of the former to potentially multiply in the environment and on the crop plant after application. The data requirements for the European Union and the United States Environmental Protection Agency are highlighted, as these regulatory processes are the most followed in regions where local regulations for biopesticide products are not available or vague. New Approach Methods already proposed or harmonized for chemical pesticides are presented and discussed with respect to their use in evaluating microbial pesticide formulations. Evaluating the microbials themselves is not as simple as using the same validated New Approach Methods as for synthetic pesticides. Therefore, the authors suggest considering New Approach Method strategies specifically for microbials and global harmonization with acceptability with the advancements of such approaches. Further discussion is needed and greatly appreciated by the experts.

Expression of genes associated with apoptosis in the porcine corpus luteum during the oestrous cycle.

The corpus luteum (CL) of the pig lacks luteolytic sensitivity (LS) to prostaglandin (PG) F-2α until after day 12 of the oestrous cycle, but the mechanisms underlying this phenomenon are poorly understood. As luteolysis involves apoptosis, we hypothesized that critical apoptotic proteins may be deficient in CLs that lack LS. The specific aim of these studies was to examine mRNA expression and protein levels of apoptosis genes/proteins (BAX/Bax, BCLX/Bcl-x, CASP3/Caspase-3, CASP8/Caspase-8, NFΚB1/NFκB, TP53/p53) in porcine CLs collected at different stages of the oestrous cycle. CLs were collected surgically, mRNA and protein extracted, and expression/levels analyzed by semi-quantitative (SQ) PCR and Western blots, respectively. At the mRNA expression level, only BAX (maximal on day 4) and TP53 (maximal on day 7) showed significant variations during the oestrous cycle. At the protein level, only Bcl-x and Caspase-3 showed significant changes during the cycle; Bcl-x decreased on day 13 and Caspase-3 increased on day 13. It is concluded that apoptosis-associated proteins (i.e. Bcl-x and Caspase 3) may play a critical role in luteolytic sensitivity in the pig.

Prospective study on cost-effectiveness of home-based motor assessment in Parkinson's disease.

Introduction Treatment adjustments in Parkinson's disease (PD) are in part dependent on motor assessments. The aim of this study was to evaluate the cost-effectiveness of home-based motor monitoring plus standard in-office visits versus in-office visits alone in patients with advanced PD. Methods The procedures consisted of a prospective, one-year follow-up, randomized, case-control study. A total of 40 patients with advanced PD were randomized into two groups: 20 patients underwent home-based motor monitoring by using wireless motion sensor technology, while the other 20 patients had in-office visits. Motor and non-motor symptom severities, quality of life, neuropsychiatric symptoms, and comorbidities were assessed every four months. Direct costs were assessed using a standardized questionnaire. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER). Results Both groups of PD patients were largely comparable in their clinical and demographic variables at baseline; however, there were more participants using levodopa-carbidopa intestinal gel in the home-based motor monitoring group. There was a trend for lower Unified Parkinson's Disease Rating Scale functional status (UPDRS II) scores in the patients monitored at home compared to the standard clinical follow-up ( p = 0.06). However, UPDRS parts I, III, IV and quality-adjusted life-years scores were similar between both groups. Home-based motor monitoring was cost-effective in terms of improvement of functional status, motor severity, and motor complications (UPDRS II, III; IV subscales), with an ICER/UPDRS ranging from €126.72 to €701.31, respectively. Discussion Home-based motor monitoring is a tool which collects cost-effective clinical information and helps augment health care for patients with advanced PD.

Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers.

OBJECTIVE: To determine whether schizophrenics and their nonschizophrenic siblings have a similar pattern of neuropsychological deficit when compared with normal controls. DESIGN AND PARTICIPANTS: Fifteen probands with schizophrenia, 16 of their nonschizophrenic siblings, and 31 unrelated, demographically balanced, normal individuals underwent evaluation with a comprehensive neuropsychological test battery. All subjects were screened for history of head injury, neurologic illness, major medical conditions, substance use, and axis I psychiatric disorders other than schizophrenia. Probands underwent evaluation twice: once at intake when half had never received neuroleptic medication and the other half had received none for a minimum of 2 weeks, and again at the 2- to 4-week follow-up, after stabilization with neuroleptic medications. RESULTS: Both schizophrenics and their nonschizophrenic siblings were impaired neuropsychologically compared with normal controls, with the nonschizophrenic siblings' performance intermediate between that of the schizophrenic siblings and the normal controls on all measures of functioning. The shapes of the deficit profiles of schizophrenic patients and their siblings were similar; in patients, verbal memory, abstraction, attention, and language functions were significantly more affected compared with spatial abilities, spatial memory, and sensory-motor functions, with a nonsignificant trend in the same direction in siblings. Cognitive functioning in patients was found to be stable across changes in medication status and clinical state. Four fifths of patients obtained more deviant scores than their nonschizophrenic siblings. Among the sibling group, those with probable and certain diagnoses of schizotypal personality disorder were more impaired compared with those without schizophrenia-spectrum symptoms. CONCLUSION: These results support the hypothesis that impaired information processing aggregates in the family members of schizophrenics and may serve as an indicator of genetic vulnerability to the disorder. Further work is needed to establish whether particular areas of functioning are selectively impaired in relatives and to determine whether the performance deficits are mediated by structural and/or metabolic disturbances in specific brain regions.

Structural brain abnormalities in schizophrenia: a family study.

Structural brain abnormalities such as ventricular enlargement are robust correlates of schizophrenia, but the degree of difference compared with unrelated normal controls is only moderate (< 1 standard deviation), and only 40% of patients have values on these measures that fall outside of the normal distribution. Family studies can help to clarify the meaning of this overlap by controlling for some of the non-schizophrenia-related genetic variation in neuroanatomical traits. Computerized tomographic scans of the brain were used to measure ventricular and sulcal cerebrospinal fluid (CSF) to brain ratios (VBR and SBR) for each hemisphere in 16 pairs of discordant siblings from the Copenhagen Schizophrenia High-Risk Project. Schizophrenics' values for VBR and SBR exceeded those of their nonschizophrenic siblings in 75% of the pairs; on average, patients' values on these measures were 1 and 5 standard deviations larger, respectively, than those of their nonschizophrenic siblings. Sulcal and left hemisphere effects were significantly more pronounced than ventricular and right hemisphere effects. After controlling for between-family variation, structural brain abnormalities appear to be more prevalent and more pronounced in schizophrenia than has previously been assumed, with relatively greater deviation observed for cortical and left hemisphere measures of CSF space enlargement.

Cross-sectional study of older outpatients with schizophrenia and healthy comparison subjects: no differences in age-related cognitive decline.

OBJECTIVE: Little is known about the progression of cognitive deficits in older, community-dwelling patients with schizophrenia, especially in comparison to healthy subjects. METHOD: The authors examined the relationship of age to performance on the Mattis Dementia Rating Scale in 116 outpatients with schizophrenia and 122 normal comparison subjects. Subjects ranged in age from 40 to 85 years. RESULTS: Dementia Rating Scale scores were lower in the schizophrenia group but correlated negatively with age in both groups, with no significant differences seen between the schizophrenia and normal comparison groups in slopes that depicted age-related variation. CONCLUSIONS: This cross-sectional study suggests a relatively stable long-term course of cognitive impairment in individuals with schizophrenia, with no evidence of faster cognitive decline in outpatients with schizophrenia than in normal comparison subjects.

Airway obstruction due to goiter in older patients.

It has been shown that goiters can progressively enlarge to compress the surrounding trachea or esophagus and result in incapacitating obstructive symptoms or potentially fatal airway obstruction. The potential of a goiter to become hyperactive also exists. Recently, we have seen three older patients with longstanding untreated "benign" goiters who presented difficult management decisions. Given the likelihood of progressive growth of a goiter and the increased life expectancy of these patients with goiters, it is essential to perform flow-volume loop studies while following these patients.

Activation of the prefrontal cortex during judgments of recency: a functional MRI study.

Animal and human lesion studies have consistently shown that damage to the prefrontal lobe disrupts performance on tasks requiring memory for temporal context. In this study, functional magnetic resonance imaging (fMRI) was used to explore the brain regions associated with judgements of relative recency in healthy humans. Bilateral dorsolateral prefrontal cortex (Brodmann's area [BA] 9) was more active during a verbal recency judgment task than during a non-mnemonic control task. Activation related to temporal context recognition was also observed in midline supplementary motor area (BA 6) and left precuneus (BA 7). This study provides further evidence that memory for temporal context requires the prefrontal cortex and is the first to demonstrate this association in healthy humans. The current findings also suggest the possibility that recognition of context and recognition of episodic content may involve similar brain systems.

Phase II trial of recombinant interferon-alpha2b in patients with advanced intractable multidrug-resistant pulmonary tuberculosis: long-term follow-up.

SETTING: Multidrug-resistant tuberculosis patients without human immunodeficiency virus (HIV) infection, with Mycobacterium tuberculosis resistant to almost all of the available drugs. OBJECTIVE: Limited phase II trial with recombinant interferon-alpha2b in five chronic multidrug-resistant tuberculosis patients. METHODS: Three million units of r-IFN-alpha2b were administered subcutaneously every week for 12 weeks. Before and after treatment, and during a 30-month follow-up period, the patients underwent clinical and radiological examination, together with bacteriological, immunological and routine laboratory testing. RESULTS: Two of the five patients became long-term sputum smear and culture negative after r-IFN-alpha2b therapy; one of the patients showed clinical improvement and negative smear after therapy, but remained culture positive. The other two patients showed no response. CONCLUSION: The results of this trial suggest that r-IFN-alpha2b should be evaluated further in multidrug-resistant tuberculosis in prospective controlled trials.

Nocturnal monitoring of growth hormone, insulin, C-peptide, and glucose in patients with acromegaly.

Circulating growth hormone, insulin, C-peptide, and glucose levels were compared during the sleep state in adults with acromegaly and healthy control subjects. Growth hormone secretion was episodic in both groups, with the sleep-related growth hormone peak noticeably absent in the acromegalic subjects. The mean nocturnal plasma insulin concentration was greater in the acromegalics. There was no significant difference in the C-peptide between the two groups. Insulin and glucose levels did not show an early morning rise in either acromegalics or healthy subjects. The authors conclude that there is a marked difference in the circulating levels of growth hormone and insulin between the acromegalic and the healthy groups during the sleep state, and there is no sleep-related nocturnal growth hormone peak in the acromegalic subjects. The hyperinsulinism of patients with acromegaly cannot be attributed to excess secretion of insulin.

Epilepsy and neurocysticercosis in a village in Huaraz, Peru.

Sixteen individuals presenting with seizures in a rural village of Peru were screened for antibodies to Taenia solium, and those willing to attend were offered a complete neurological work-up including EEG and cerebral CT scan in a reference center. Seroprevalence using immunoblot was 35% (5/16). Eight individuals came for examination. CT scans were abnormal in all four seropositive cases (an enhancing lesion in one case, multiple live cysts and calcifications in one case, and multiple calcifications in two cases), and normal in the four seronegative individuals. Electroencephalographic tracings were normal in six cases, and abnormal in one seronegative and in one seropositive individual. Neurocysticercosis (NCC) is frequently found in epileptic individuals in most developing countries, and is probably the major cause of seizures in this zone.

[Evaluation and treatment of interstitial lung disease in Argentine]. / Evaluación y tratamiento de la enfermedad intersticial pulmonar en la Argentina.

To determine the availability and usual management of interstitial lung diseases (ILD) in our country, the Section of Interstitial Lung Diseases of the Argentine Association for Respiratory Medicine (AAMR) made a survey about diagnostic methodology and treatment of ILD. A total of 115 answers were obtained (38.5%), 43% of them among physicians living in the provinces. Availability of diffusing capacity of the lung for carbon monoxide test (DLCO) is limited: 25.4% never have access to it and 35.6% can seldom use it. Availability to thoracic CT scan is wider: 85% may use if often (32.4%) or always (52.6%). Bronchoscopy is commonly available in 87.7% of the physicians either often (21.9%) or always (65.8%). However, only 20.2% perform BAL and 13.1% transbronchial biopsy in every patient. Only 16.6% perform open lung biopsy or thoracoscopic biopsy in all or most of their patients. Sixty eight percent of physicians who always have availability of DLCO perform it in every patient but only 7.1% of those who seldom have access to DLCO do so (p = 0.0003). Availability of bronchoscopy does not have any influence on the decision of performing BAL or transbronchial biopsy. Frequency of use of surgical biopsy or treatment with immunosuppressive drugs was not influenced by any variable. We conclude that there is a current trend to underuse diagnostic resources for ILD in Argentina. Limitations in availability are relevant regarding DLCO. An effort from the health authorities to centralize the management of patients with ILD would allow to study and treat them according to international recommendations.

Endothelin-1, endothelin converting enzyme-1 and endothelin receptors in the porcine corpus luteum.

Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2alpha (PGF-2alpha) (ie, luteolytic sensitivity [LS]) until about day 12-13 of the estrous cycle. Although little is known of the control of LS in any species, endothelin-1 (EDN1) is believed to play a role in LS control in ruminants. Therefore, we measured mRNA and protein expression and examined the cellular localization of EDN1 precursor (pre-pro EDN1, or ppEDN1), EDN-converting enzyme-1 (ECE1), and EDN receptors (A, EDNRA and B, EDNRB) in porcine CLs collected on days 4, 7, 10, 13, and 15 of the estrous cycle to look for differences between CLs displaying (days 13-15) versus those lacking (days 4-10) LS. Abundance of ppEDN1 mRNA was greatest (and significant vs all other days) on day 7 of the cycle, whereas EDN1 protein expression did not vary during the cycle and was localized exclusively to endothelial cells (EC). Abundance of ECE1 mRNA was also greatest on day 7 (vs all other days), but ECE1 protein was significantly elevated on day 10 (vs day 4) and was immunolocalized to ECs and large luteal cells (LLC). Abundance of EDNRA mRNA was also maximal on day 7 (vs all other days) of the cycle, whereas EDNRA protein expression was not significantly changed during the cycle and was observed in LLCs, ECs, and small luteal cells (SLC). On day 13, EDNRB mRNA was significantly decreased (versus day 7). Expression of EDNRB protein was decreased on day 10 (versus all other days), and on days 13-15 (vs day 4), and was primarily localized to ECs. In conclusion, the observed elevation in ECE1 protein concentrations on day 10 and the presence of EDNRA on LLC suggests a possible role for EDN1 (resulting from the actions of ECE1) acting via EDNRA in the control of LS in the pig.

Protein kinase C isoforms in the porcine corpus luteum: temporal and spatial expression patterns.

Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2alpha (PGF-2alpha) (ie, luteolytic sensitivity, or LS) until approximately day 13 of the estrous cycle. In view of the importance of protein kinase C (PRKC) in PGF-2alpha signal transduction, it was hypothesized that limiting levels of 1 or more PRKC isoforms may explain the lack of LS before day 13. This hypothesis was tested by examining expression of mRNA and protein, and the cellular localization patterns of the 11 PRKC isoforms throughout the porcine estrous cycle, to determine whether PRKC expression correlates with and thus may be associated with the control of the acquisition of LS in the pig. The expression patterns show that for most PRKC isoforms (ie, PRKC alpha, beta 1, beta 2, delta, epsilon, theta, iota, and zeta), mRNA was maximally expressed on day 7 or day 10 (protein kinase D1 only) of the cycle, whereas PRKCs gamma, eta, and lambda were unchanged. At the protein level, only PRKC epsilon (PRKCE) significantly changed during the estrous cycle and was elevated on day 13 (versus days 4, 7, and 15; P<0.05). By immunofluoresence, most PRKC isoforms, including PRKCE, were localized to steroidogenic large luteal cells (LLC) and small (nonendothelial cell) luteal cell subtypes (SLC). In conclusion, since the increase in PRKCE protein expression (day 13) occurred coincidentally with the onset of LS (> or =day 12), these results support a potential role for PRKCE in control of the acquisition of LS in the pig.

Functional evaluation of the shoulder following latissimus dorsi muscle transfer.

The dynamic muscle function of the shoulder in 26 patients (10 males, 16 females) who underwent a pedicled or free vascularized latissimus dorsi muscle transfer between 1985 and 1991 (mean follow-up, 4.4 yr) was studied. Instrumented muscle testing was performed on the Kinetic Communicator machine (Kin Com) and the Baltimore Therapeutic Equipment (BTE) work simulator. The female unilateral pedicle group (n = 13) showed a significant difference between operated and nonoperated shoulders for both peak torque (power) and work (endurance) measurements of shoulder adduction and extension on the Kin Com (mean ratios operated/nonoperated shoulders, 55% to 69%). They also showed significant differences for work performance on three of four BTE tests (mean ratios, 77% to 84%). The male free vascularized group (n = 10) similarly showed a significant deficit of both peak torque and work for shoulder extension and adduction on the Kin Com (mean ratios, 74% to 84%); however, they showed no deficit on the BTE tests. In conclusion, dynamic muscle tests demonstrate a deficit of muscle power and endurance of shoulder extension and adduction following latissimus dorsi muscle transfer.

Aging and outcome in schizophrenia.

OBJECTIVE: Controversy exists about long-term outcome of schizophrenia, but few studies have compared older out-patients to normal subjects. We sought to examine the relationship of age to clinical features, psychopathology, movement abnormalities, quality of well-being, and everyday functioning in schizophrenia out-patients and normal comparison subjects, and to further characterize these outcomes in elderly schizophrenia out-patients. METHOD: A total of 290 out-patients and 144 comparison subjects, aged 40-85 years, underwent comprehensive assessments. RESULTS: Among patients, aging was associated with decreased psychopathology, even after controlling for duration of illness. There was no accelerated aging-related decline on any measure in the patients. Yet, elderly patients were more impaired than comparison subjects on various measures. CONCLUSION: The course of schizophrenia in late life appears stable, but most elderly patients remain symptomatic and impaired. Our findings dispute notions of either progressive deterioration or marked improvement in aging schizophrenia out-patients.