Suffering in silence: How COVID-19 school closures inhibit the reporting of child maltreatment.

To combat the spread of COVID-19, many primary and secondary schools in the United States canceled classes and moved instruction online. This study examines an unexplored consequence of COVID-19 school closures: the broken link between child maltreatment victims and the number one source of reported maltreatment allegations-school personnel. Using current, county-level data from Florida, we estimate a counterfactual distribution of child maltreatment allegations for March and April 2020, the first two months in which Florida schools closed. While one would expect the financial, mental, and physical stress due to COVID-19 to result in additional child maltreatment cases, we find that the actual number of reported allegations was approximately 15,000 lower (27%) than expected for these two months. We leverage a detailed dataset of school district staffing and spending to show that the observed decline in allegations was largely driven by school closures. Finally, we discuss policy implications of our findings for the debate surrounding school reopenings and suggest a number of responses that may mitigate this hidden cost of school closures.

Independent or simultaneous lowering of core and skin temperature has no impact on self-paced intermittent running performance in hot conditions.

PURPOSE: To investigate the effects of lowering core (Tgi) and mean skin temperature (Tsk) concomitantly and independently on self-paced intermittent running in the heat. METHODS: 10 males (30.5 ± 5.8 years, 73.2 ± 14.5 kg, 176.9 ± 8.0 cm, 56.2 ± 6.6 ml/kg/min) completed four randomised 46-min self-paced intermittent protocols on a non-motorised treadmill in 34.4 ± 1.4 °C, 36.3 ± 4.6% relative humidity. 30-min prior to exercise, participants were cooled via either ice slurry ingestion (INT); a cooling garment (EXT); mixed-cooling (ice slurry and cooling garment concurrently) (MIX); or no-cooling (CON). RESULTS: At the end of pre-cooling and the start of exercise Tgi were lower during MIX (36.11 ± 1.3 °C) compared to CON (37.6 ± 0.5 °C) and EXT (36.9 ± 0.5 °C, p < 0.05). Throughout pre-cooling Tsk and thermal sensation were lower in MIX compared to CON and INT, but not EXT (p < 0.05). The reductions in thermophysiological responses diminished within 10-20 min of exercise. Despite lowering Tgi, Tsk, body temperature (Tb), and thermal sensation prior to exercise, the distances covered were similar (CON: 6.69 ± 1.08 km, INT: 6.96 ± 0.81 km, EXT: 6.76 ± 0.65 km, MIX 6.87 ± 0.70 km) (p > 0.05). Peak sprint speeds were also similar between conditions (CON: 25.6 ± 4.48 km/h, INT: 25.4 ± 3.6 km/h, EXT: 26.0 ± 4.94 km/h, MIX: 25.6 ± 3.58 km/h) (p > 0.05). Blood lactate, heart rate and RPE were similar between conditions (p > 0.05). CONCLUSION: Lowering Tgi and Tsk prior to self-paced intermittent exercise did not improve sprint, or submaximal running performance.

The relationship between interleukin-6 in saliva, venous and capillary plasma, at rest and in response to exercise.

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). In Trial A venous plasma IL-6 increased significantly from 0.4±0.14pg/ml to 0.99±0.29pg/ml (P<0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22±0.18 to 0.74±0.28pg/ml (P⩽0.01); capillary: 0.37±0.22 to 1.08±0.30pg/ml (P<0.01). Venous and capillary plasma responses did not correlate at rest (r=0.59, P=0.07) but did correlate post exercise (r=0.79, P⩾0.001) and when expressed as an exercise induced change (r=0.71, P=0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.

Challenging behaviour and sleep cycle disorder following brain injury: a preliminary response to agomelatine treatment.

BACKGROUND: Sleep disturbances are common after acquired brain injury. Sedatives can exacerbate behavioural disorders. OBJECTIVES: This study reports the case of a severely brain damaged man (TM) who developed a non-24 hour sleep cycle disorder that was effectively managed by the administration of a melatonin receptor agonist, agomelatine. METHOD: TM suffered significant brain damage as a result of a large subarachnoid haemorrhage of his right anterior cerebral artery complicated by midline shift and subsequent infarction of his left middle cerebral artery. In addition to challenging behaviour and cognitive impairment, TM presented with a recurrent disturbed sleep-wake pattern that significantly worsened his quality-of-life. He was diagnosed as suffering of non-24 hour sleep-wake disorder. Challenge was recorded using the Overt Aggression Scale Modified for Neuro-Rehabilitation (OASMNR). RESULTS: Typical hypnotics had no or ill effects. Agomelatine prescription (25 mg) led to significant OASMNR and sleep efficiency change with effects apparent at 1.5 years later. CONCLUSIONS: Administration of the melatonin receptor (MT1 and MT2) agonist agomelatine each night resulted in an immediate and sustained improvement on sleep and on indices of challenging behaviour.

Axis dependent conduction polarity in the air-stable semiconductor, PdSe2.

Axis-dependent conduction polarity (ADCP) is a unique electronic phenomena in which the charge polarity of carrier conduction can differ from p-type to n-type depending on the direction of travel through the crystal. Most materials that exhibit ADCP are metals, and very few semiconducting materials exhibit this effect. Here, we establish that PdSe2, a ∼0.5 eV band gap semiconductor that is air- and water-stable, exhibits ADCP, through the growth and characterization of the transport properties of crystals with extrinsic p- and n-type doping levels of Ir and Sb, respectively, in the 1016-1018 cm-3 range. Electron doped PdSe2 exhibits p-type conduction in the cross-plane direction and n-type conduction along the in-plane directions above an onset temperature of 100-200 K that varies with doping level. Lightly p-doped samples show p-type thermopower in all directions at low temperatures, but above ∼360 K the in-plane thermopower turns negative. Density functional theory calculations indicate that the origin of ADCP arises from the complementary effective mass anisotropies in the valence and conduction bands in this material, which facilitate hole transport in the cross-plane direction, and electron transport along the in-plane directions. ADCP occurs at temperatures with sufficient thermal population of both carrier types to overcome the extrinsic doping levels to exploit the effective mass anisotropy. In total, the development of this stable semiconductor in which thermally or optically excited holes and electrons inherently migrate along different directions opens up numerous potential applications in a multitude of technologies.

Design of microresonators to minimize thermal noise below the standard quantum limit.

Microfabricated resonators play a crucial role in the development of quantum measurement, including future gravitational wave detectors. We use a micro-genetic algorithm and a finite element method to design a microresonator whose geometry is optimized to maximize the sub-Standard Quantum Limit (SQL) performance including lower thermal noise (TN) below the SQL, a broader sub-SQL region, and a sub-SQL region at lower frequencies. For the proposed design, we study the effects of different geometries of the mirror pad and cantilever microresonator on sub-SQL performance. We find that the maximum ratio of SQL to TN is increased, its frequency is decreased, and the sub-SQL range is increased by increasing the length of the microresonator cantilever, increasing the radius of the mirror pad, decreasing the width of the microresonator cantilever, and shifting the laser beam location from the mirror center. We also find that there exists a trade-off between the maximum ratio of SQL to TN and the sub-SQL bandwidth. The performance of this designed microresonator will allow it to serve as a test-bed for quantum non-demolition measurements and to open new regimes of precision measurement that are relevant for many practical sensing applications, including advanced gravitational wave detectors.

Variable Refocusing Flip Angle Single-Shot Imaging for Sedation-Free Fast Brain MRI.

BACKGROUND AND PURPOSE: Conventional single-shot FSE commonly used for fast MRI may be suboptimal for brain evaluation due to poor image contrast, SNR, or image blurring. We investigated the clinical performance of variable refocusing flip angle single-shot FSE, a variation of single-shot FSE with lower radiofrequency energy deposition and potentially faster acquisition time, as an alternative approach to fast brain MR imaging. MATERIALS AND METHODS: We retrospectively compared half-Fourier single-shot FSE with half- and full-Fourier variable refocusing flip angle single-shot FSE in 30 children. Three readers reviewed images for motion artifacts, image sharpness at the brain-fluid interface, and image sharpness/tissue contrast at gray-white differentiation on a modified 5-point Likert scale. Two readers also evaluated full-Fourier variable refocusing flip angle single-shot FSE against T2-FSE for brain lesion detectability in 38 children. RESULTS: Variable refocusing flip angle single-shot FSE sequences showed more motion artifacts (P < .001). Variable refocusing flip angle single-shot FSE sequences scored higher regarding image sharpness at brain-fluid interfaces (P < .001) and gray-white differentiation (P < .001). Acquisition times for half- and full-Fourier variable refocusing flip angle single-shot FSE were faster than for single-shot FSE (P < .001) with a 53% and 47% reduction, respectively. Intermodality agreement between full-Fourier variable refocusing flip angle single-shot FSE and T2-FSE findings was near-perfect (κ = 0.90, κ = 0.95), with an 8% discordance rate for ground truth lesion detection. CONCLUSIONS: Variable refocusing flip angle single-shot FSE achieved 2× faster scan times than single-shot FSE with improved image sharpness at brain-fluid interfaces and gray-white differentiation. Such improvements are likely attributed to a combination of improved contrast, spatial resolution, SNR, and reduced T2-decay associated with blurring. While variable refocusing flip angle single-shot FSE may be a useful alternative to single-shot FSE and, potentially, T2-FSE when faster scan times are desired, motion artifacts were more common in variable refocusing flip angle single-shot FSE, and, thus, they remain an important consideration before clinical implementation.

A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins.

To examine the function of the alpha 6 beta 4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that alpha 6 beta 4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-beta 1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous alpha 6 beta 4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail-less beta 4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less beta 4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head-less mutant beta 4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that alpha 6 beta 4-mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin.

A combined analysis of 2 randomized clinical studies of tretinoin gel 0.05% for the treatment of acne.

Acne vulgaris is a widely prevalent skin disorder primarily treated with retinoids, which have been shown to cause skin irritation. This report describes the combined analysis of 2 similar phase 3 studies designed to evaluate the efficacy and safety of an aqueous gel formulation of tretinoin relative to its vehicle (both studies) and a marketed microsphere formulation of tretinoin (one study) for once-daily topical treatment of acne. Randomized participants 10 years and older with mild to moderate acne (N=1537) received tretinoin gel 0.05% (n=674), tretinoin gel microsphere 0.1% (n=376), or vehicle (n=487) once daily for 12 weeks. Tretinoin gel was more effective than vehicle in reducing inflammatory (P<.001) and noninflammatory (P<.001) lesion counts over 12 weeks. Treatment success rate (global severity score, 0 or 1) was significantly greater in the tretinoin gel 0.05% group compared with the vehicle group (P<.001). The efficacy rate of tretinoin gel 0.05% was approximately 12% less than tretinoin gel microsphere 0.1%. Adverse events (AEs) were generally mild to moderate and rarely resulted in participant discontinuation. Incidence of skin-related AEs in the tretinoin gel 0.05% group (31%) was significantly lower compared with the tretinoin gel microsphere 0.1% group (52%)(P<.001). Thus, tretinoin gel 0.05% applied once daily is a well-tolerated and effective therapy for acne vulgaris and is associated with a low incidence of skin-related AEs.

Stable isotopic characterization of a coastal floodplain forest community: a case study for isotopic reconstruction of Mesozoic vertebrate assemblages.

Stable isotopes are powerful tools for elucidating ecological trends in extant vertebrate communities, though their application to Mesozoic ecosystems is complicated by a lack of extant isotope data from comparable environments/ecosystems (e.g. coastal floodplain forest environments, lacking significant C4 plant components). We sampled 20 taxa across a broad phylogenetic, body size, and physiological scope from the Atchafalaya River Basin of Louisiana as an environmental analogue to the Late Cretaceous coastal floodplains of North America. Samples were analysed for stable carbon, oxygen and nitrogen isotope compositions from bioapatite and keratin tissues to test the degree of ecological resolution that can be determined in a system with similar environmental conditions, and using similar constraints, as those in many Mesozoic assemblages. Isotopic results suggest a broad overlap in resource use among taxa and considerable terrestrial-aquatic interchange, highlighting the challenges of ecological interpretation in C3 systems, particularly when lacking observational data for comparison. We also propose a modified oxygen isotope-temperature equation that uses mean endotherm and mean ectotherm isotope data to more precisely predict temperature when compared with measured Atchafalaya River water data. These results provide a critical isotopic baseline for coastal floodplain forests, and act as a framework for future studies of Mesozoic palaeoecology.

Perception and quality of life associated with the use of olopatadine 0.2% (Pataday) in patients with active allergic conjunctivitis.

This 28-d, open-label, multicenter, single-arm clinical study was designed to evaluate perceptions of olopatadine 0.2% in patients with active ocular allergic signs and symptoms. The study enrolled 330 patients, 5 to 94 y of age, who had previously used olopatadine 0.1% for active allergic conjunctivitis. Most patients were white (n=230; 70.1%) and female (n=239; 72.9%). Of all enrolled patients, 328 were evaluable for analysis. Throughout the study, patients instilled 1 drop of olopatadine 0.2% into each eye once daily; adverse events were documented and ocular evaluations were conducted to ensure patient safety. Direct evaluations of efficacy were not performed. On days 1 and 7, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire, recorded their perceptions of olopatadine 0.1% (day 1) or 0.2% (day 7), and had their ocular allergies assessed globally. On each of the first 6 d of treatment, patients also completed a telephone-based perception questionnaire. On day 28, patients returned to the study center, reported their treatment perceptions, had their ocular allergies assessed, and exited the trial. Overall, patients had a positive perception of olopatadine 0.2%. Patients were more satisfied with olopatadine 0.2% than they remembered being with olopatadine 0.1% (289 vs 257 patients; 87.6% vs 77.8%; P<.05). The majority of the 48 patients who wore contact lenses (n=42; 88%) believed that they could wear their contacts as desired. Significant improvement was noted in all categories of the Rhinoconjunctivitis Quality of Life Questionnaire (P<.0001). No unexpected safety findings were reported. Patients perceived olopatadine 0.2% to be effective and well tolerated.

Insights about Fall Prevention of Older Adults in the State of Hawai'i.

The senior population in Hawai'i is growing at a dramatic pace. In the older population, falls and fall-related injuries are leading causes of morbidity and mortality. Moreover, the health care costs for falls are very high. The State of Hawai'i has taken measures to prevent falls through the promotion of medication reviews, vision checks, home assessments, and exercise. However, current published examinations of fall preventive measures have been insufficient, and more research is needed to confirm risk factors, effectiveness of preventive measures, and to explore future objectives. This paper examined the validity of fall risk factors and fall preventive measures for Hawai'i's seniors by conducting mail questionnaire surveys to a sample of seniors using medical alert services from one company in Hawai'i. The results of chi-square analysis suggest that having reduced ability to perform Activities of Daily Living (ADL) and reduced Instrumental Activities of Daily Living (IADL) were associated with a greater risk of falls (P < .01). In addition, those who fell were more likely to talk about fall preventions with their family members or friends and health providers compared with those who did not (P = .048 and .003, respectively). Evidence-based exercise programs for strengthening muscles and controlling physical balance may be needed to improve ADL and IADL. Furthermore, the results suggest that seniors do not accept that they are at risk of falling before they actually fall. Public health providers should consider how they approach seniors, and how they inform them of the importance of fall prevention across the life span.

Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis.

BACKGROUND: A new formulation of olopatadine hydrochloride ophthalmic solution (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled, double-masked, hybrid environmental studies intended to determine efficacy and safety in subjects with histories of seasonal allergic conjunctivitis or rhinoconjunctivitis. DESIGN AND METHODS: In these 10- and 12-week trials (conducted April-August 2003 and July-December 2001, respectively), subjects assessed their ocular signs and symptoms. Additionally, subjects in the 10-week trial evaluated the frequency of their nasal symptoms while subjects in the 12-week trial evaluated both the frequency and severity of their nasal symptoms. The two trials had a combined enrollment of 500 subjects (217 males, 283 females) including 44 children aged 10-17 years; the combined population was 81.4% Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these studies, either ragweed (fall study) or grass (spring study) pollen counts were obtained from each investigative center. Slope analyses were conducted on the nasal symptom assessments by pollen count. RESULTS: The nasal results from the two clinical trials are presented herein. In the fall study, relative to placebo, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031) relative to placebo. In the fall trial, 2 subjects discontinued due to treatment-related adverse events (tachycardia and dry eye), while in the spring study, no subject discontinued due to a treatment-related adverse event. No subject in either study suffered a treatment-related serious adverse event. CONCLUSIONS: For the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe, well-tolerated, and effective in significantly reducing the frequency and/or severity of some effects of pollen on nasal symptoms.

Gut microbiota. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation.

Resilience to host inflammation and other perturbations is a fundamental property of gut microbial communities, yet the underlying mechanisms are not well understood. We have found that human gut microbes from all dominant phyla are resistant to high levels of inflammation-associated antimicrobial peptides (AMPs) and have identified a mechanism for lipopolysaccharide (LPS) modification in the phylum Bacteroidetes that increases AMP resistance by four orders of magnitude. Bacteroides thetaiotaomicron mutants that fail to remove a single phosphate group from their LPS were displaced from the microbiota during inflammation triggered by pathogen infection. These findings establish a mechanism that determines the stability of prominent members of a healthy microbiota during perturbation.

Isosexual precocious pseudopuberty secondary to a feminizing adrenal tumor.

We report a 2 10/12-yr-old girl with precocious pseudopuberty due to a feminizing adrenal carcinoma without Cushing's syndrome. The patient had marked elevation of plasma concentrations of the delta 5 adrenal steroids dehydroepiandosterone and dehydroepiandrosterone sulfate and increased levels of androstenedione, estrone, estradiol, and testosterone. Adrenal microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase 17-hydroxylase, 17,20-desmolase, and 21-hydroxylase activities in the tumor and adjacent normal adrenal gland were measured. The tumor had approximately normal levels of 17-hydroxylase and 17,20-desmolase activity, with low levels of 21-hydroxylase and 3 beta-hydroxysteroid dehydrogenase-isomerase activities. This combination of enzyme activity may explain the absence of Cushing's syndrome and the high levels of delta 5 adrenal steroids. This patient demonstrates that adrenal neoplasms arising in girls may mimic isosexual true precocious puberty and should be included in the differential diagnosis of precocious puberty.

Platelet counts in capillary blood.

Samples of venous and capillary blood were collected simultaneously from healthy adults to assess the accuracy of platelet counts in capillary blood as determined by an automated particle counter. The difference between the mean venous blood platelet count (248,300) and the mean capillary blood count (215,500) was highly significant (P less than .001). For 24% (7/29) of the subjects, the capillary blood platelet count underestimated the venous blood count by greater than or equal to 25%, with three subjects erroneously classified as thrombocytopenic. A heterogeneous group of thrombocytopenic patients showed a similar difference in mean platelet counts (venous blood: 72,500/microliter; capillary blood: 65,400/microliter; P = 0.01). In most clinical situations, capillary blood platelet counts were adequate for patient evaluation; however, when an accurate platelet count is necessary, venous blood should be used.

A postmortem study of the mediodorsal nucleus of the thalamus in schizophrenia.

Four studies have reported that the mediodorsal nucleus of the thalamus (MD) is smaller and contains fewer neurons in schizophrenia. The MD is a key node in a circuit proposed to be dysfunctional in the disorder. However, one study did not find a MD volume loss in schizophrenia, and all the studies to date are relatively small. Given the importance of establishing unequivocally the presence of MD pathology, we have carried out a study of the volume and number of neurons in the left and right MD in 21 patients with schizophrenia and 27 healthy comparison subjects. We also measured the size of MD neurons, and estimated total thalamic volume. We found no difference in the volume of the MD, the number of MD neurons, or the size of MD neurons in either hemisphere in schizophrenia. Neither was total thalamic volume altered. There are no obvious methodological or clinical factors to explain our failure to replicate the finding of MD involvement in schizophrenia. Hence our negative observations, in the largest sample yet investigated, cast doubt on the robustness and/or the generalisability of MD neuropathology in schizophrenia.

Clinical efficacy of olopatadine hydrochloride ophthalmic solution 0.2% compared with placebo in patients with allergic conjunctivitis or rhinoconjunctivitis: a randomized, double-masked environmental study.

BACKGROUND: Previous studies have suggested that olopatadine hydrochloride ophthalmic solution 0.2% administered once daily is effective for up to 24 hours after instillation and is well tolerated in adults and children aged > or =3 years. OBJECTIVE: The goal of this study was to evaluate the efficacy and safety profile of olopatadine 0.2% compared with placebo in patients with seasonal allergic conjunctivitis or rhinoconjunctivitis. METHODS: This was a 10-week, randomized, placebo-controlled, double-masked environmental study conducted during the spring allergy season (April-August) of 2003. Patients assessed their ocular signs and symptoms in terms of frequency (whole-unit scale from 0 to 5) and severity (half-unit scale from 0 to 4), and grass pollen counts were obtained daily for each investigative site. Responder analyses were conducted by pollen level (frequency based) and pollen period (severity based) to evaluate the clinical significance of differences in ocular itching and redness between treatment groups. RESULTS: Two hundred sixty patients (137 females, 123 males) were enrolled in the study, including 28 children aged between 11 and 17 years; the overall population was 74% white, 11% black, 4% Hispanic, and 11% other. The frequency-based responder analyses of ocular itching and redness showed that when grass pollen counts were high (>20 gr/m(3) air), a respective 21% and 14% of patients in the olopatadine 0.2% group assessed the frequency of ocular itching and redness as >2, compared with 47% and 31% of patients in the placebo group (P < 0.001 for ocular itching; P < 0.003 for redness). The results of the severity-based responder analyses by peak pollen period were consistent with those of the frequency-based analyses. Compared with placebo, olopatadine 0.2% was associated with significant reductions in calculated mean scores for ocular itching and redness by pollen level and by pollen period. No patient was discontinued from the study because of a treatment-related adverse event, and no patient experienced a treatment-related serious adverse event. CONCLUSION: In the patients studied, olopatadine 0.2% appeared to be effective and well tolerated when administered once daily for the treatment of the ocular signs and symptoms of allergic conjunctivitis or rhinoconjunctivitis.

Intranigral or intrastriatal injections of GDNF: effects on monoamine levels and behavior in rats.

The present studies were designed to determine whether administration of recombinant human glial cell line-derived neurotrophic factor (rhGDNF) into either the substantia nigra or striatum is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats. Single bolus intracranial injections of rhGDNF at either site increased locomotor activity and decreased food and water consumption and body weight in a dose-dependent manner when compared to vehicle-treated animals. These behavioral responses returned to pre-control levels within 3 weeks post rhGDNF administration. Administration of rhGDNF intranigrally increased dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels of the ipsilateral substantia nigra at 2 and 6 weeks post injection but had no augmenting effects on dopamine or its metabolites in the striatum. Administration of rhGDNF intrastriatally increased DOPAC and HVA levels of the ipsilateral striatum, although striatal dopamine levels were unchanged. Ipsilateral nigral dopamine levels were increased after intrastriatal injection of rhGDNF. The effects of intracranial rhGDNF were not specific to the nigrostriatal dopamine system, since nigrostriatal serotonin, 5-hydroxyindoleacetic acid (5-HIAA), epinephrine and norepinephrine transmitter levels were altered depending on administration route for rhGDNF and dose. Taken together, these data demonstrate long-lasting neurochemical and behavioral changes which suggest that rhGDNF can augment function in adult rat dopamine neurons. Therefore, rhGDNF may have therapeutic potential for Parkinson's disease.

Comparing the characteristics of schools that produce high percentages and low percentages of primary care physicians.

To examine whether the medical school environment is important in influencing students to choose careers in primary care, the authors in 1991 compared certain characteristics of the environments of schools that produced high percentages of primary care physicians with those of schools that produced low percentages over a five-year period. The authors used the American Medical Association Physician Masterfile to identify the percentage of graduates of each of 121 medical schools for the period 1981-1985 who entered primary care specialties. They then compared the 25 schools that produced low percentages (22-29%) with the 25 schools that produced high percentages (39-56%). The results demonstrate important differences between the two groups of schools in their commitments to primary care education, their research programs, and their clinical environments supporting required clerkships. The authors conclude that a school's educational environment is an important factor in influencing some students to pursue careers in primary care medicine.