Multidisciplinary Center Care for Long COVID Syndrome-A Retrospective Cohort Study.

BACKGROUND: Persistent multi-organ symptoms after coronavirus disease 2019 (COVID-19) have been termed "long COVID" or "post-acute sequelae of SARS-CoV-2 infection." The complexity of these clinical manifestations posed challenges early in the pandemic as different ambulatory models formed out of necessity to manage the influx of patients. Little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers. METHODS: We performed a retrospective cohort study of patients evaluated at our multidisciplinary comprehensive COVID-19 center in Chicago, Ill, between May 2020 and February 2022. We analyzed specialty clinic utilization and clinical test results according to severity of acute COVID-19. RESULTS: We evaluated 1802 patients a median of 8 months from acute COVID-19 onset, including 350 post-hospitalization and 1452 non-hospitalized patients. Patients were seen in 2361 initial visits in 12 specialty clinics, with 1151 (48.8%) in neurology, 591 (25%) in pulmonology, and 284 (12%) in cardiology. Among the patients tested, 742/878 (85%) reported decreased quality of life, 284/553 (51%) had cognitive impairment, 195/434 (44.9%) had alteration of lung function, 249/299 (83.3%) had abnormal computed tomography chest scans, and 14/116 (12.1%) had elevated heart rate on rhythm monitoring. Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19. Non-hospitalized patients with positive SARS-CoV-2 testing had findings similar to those with negative or no test results. CONCLUSIONS: The experience at our multidisciplinary comprehensive COVID-19 center shows common utilization of multiple specialists by long COVID patients, who harbor frequent neurologic, pulmonary, and cardiologic abnormalities. Differences in post-hospitalization and non-hospitalized groups suggest distinct pathogenic mechanisms of long COVID in these populations.

Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.

OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients. METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021. RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients. INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.

Ecological consequences of neonicotinoid mixtures in streams.

Neonicotinoid mixtures are common in streams worldwide, but corresponding ecological responses are poorly understood. We combined experimental and observational studies to narrow this knowledge gap. The mesocosm experiment determined that concentrations of the neonicotinoids imidacloprid and clothianidin (range of exposures, 0 to 11.9 µg/liter) above the hazard concentration for 5% of species (0.017 and 0.010 µg/liter, respectively) caused a loss in taxa abundance and richness, disrupted adult emergence, and altered trophodynamics, while mixtures of the two neonicotinoids caused dose-dependent synergistic effects. In 85 Coastal California streams, neonicotinoids were commonly detected [59% of samples (n = 340), 72% of streams], frequently occurred as mixtures (56% of streams), and potential toxicity was dominated by imidacloprid (maximum = 1.92 µg/liter) and clothianidin (maximum = 2.51 µg/liter). Ecological responses in the field were consistent with the synergistic effects observed in the mesocosm experiment, indicating that neonicotinoid mixtures pose greater than expected risks to stream health.

Common insecticide disrupts aquatic communities: A mesocosm-to-field ecological risk assessment of fipronil and its degradates in U.S. streams.

Insecticides in streams are increasingly a global concern, yet information on safe concentrations for aquatic ecosystems is sparse. In a 30-day mesocosm experiment exposing native benthic aquatic invertebrates to the common insecticide fipronil and four degradates, fipronil compounds caused altered emergence and trophic cascades. Effect concentrations eliciting a 50% response (EC50) were developed for fipronil and its sulfide, sulfone, and desulfinyl degradates; taxa were insensitive to fipronil amide. Hazard concentrations for 5% of affected species derived from up to 15 mesocosm EC50 values were used to convert fipronil compound concentrations in field samples to the sum of toxic units (∑TUFipronils). Mean ∑TUFipronils exceeded 1 (indicating toxicity) in 16% of streams sampled from five regional studies. The Species at Risk invertebrate metric was negatively associated with ∑TUFipronils in four of five regions sampled. This ecological risk assessment indicates that low concentrations of fipronil compounds degrade stream communities in multiple regions of the United States.

Uranium Bioaccumulation Dynamics in the Mayfly Neocloeon triangulifer and Application to Site-Specific Prediction.

Little is known about the underlying mechanisms governing the bioaccumulation of uranium (U) in aquatic insects. We experimentally parameterized conditional rate constants for aqueous U uptake, dietary U uptake, and U elimination for the aquatic baetid mayfly Neocloeon triangulifer. Results showed that this species accumulates U from both the surrounding water and diet, with waterborne uptake prevailing. Elevated dietary U concentrations decreased feeding rates, presumably by altering food palatability or impairing the mayfly's digestive processes, or both. Nearly 90% of the accumulated U was eliminated within 24 h after the waterborne exposure ceased, reflecting the desorption of weakly bound U from the insect's integument. To examine whether the experimentally derived rate constants for N. triangulifer could be generalized to baetid mayflies, mayfly U concentrations were predicted using the water chemistry and U measured in periphyton from springs in Grand Canyon (United States) and were compared to U concentrations in spring-dwelling mayflies. Predicted and observed mayfly U concentrations were in good agreement. Under the modeled site-specific conditions, waterborne U uptake accounted for 52-93% of the bioaccumulated U. U accumulation was limited in these wild populations due to a combination of factors including low concentrations of bioavailable dissolved U species, slow U uptake rates from food, and fast U elimination.

Bioaccumulation and Toxicity of Cadmium, Copper, Nickel, and Zinc and Their Mixtures to Aquatic Insect Communities.

We describe 2 artificial stream experiments that exposed aquatic insect communities to zinc (Zn), copper (Cu), and cadmium (year 2014) and to Zn, Cu, and nickel (year 2015). The testing strategy was to concurrently expose insect communities to single metals and mixtures. Single-metal tests were repeated to evaluate the reproducibility of the methods and year-to-year variability. Metals were strongly accumulated in sediments, periphyton, and insect (caddisfly) tissues, with the highest concentrations occurring in periphyton. Sensitive mayflies declined in metal treatments, and effect concentrations could be predicted effectively from metal concentrations in either periphyton or water. Most responses were similar in the replicated tests, but median effect concentration values for the mayfly Rhithrogena sp. varied 20-fold between the tests, emphasizing the difficulty comparing sensitivities across studies and the value of repeated testing. Relative to the single-metal responses, the toxicity of the mixtures was either approximately additive or less than additive when calculated as the product of individual responses (response addition). However, even less-than-additive relative responses were sometimes greater than responses to similar concentrations tested singly. The ternary mixtures resulted in mayfly declines at concentrations that caused no declines in the concurrent single-metal tests. When updating species-sensitivity distributions (SSDs) with these results, the mayfly responses were among the most sensitive 10th percentile of available data for all 4 metals, refuting older literature placing mayflies in the insensitive portion of metal SSDs. Testing translocated aquatic insect communities in 30-d artificial streams is an efficient approach to generate multiple species effect values under quasi-natural conditions that are relevant to natural streams. Environ Toxicol Chem 2020;39:812-833. Published 2020 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America.

Benthic algal (periphyton) growth rates in response to nitrogen and phosphorus: Parameter estimation for water quality models.

Nitrogen (N) and phosphorus (P) are significant pollutants that can stimulate nuisance blooms of algae. Water quality models (e.g., WASP, CE-QUAL-R1, CE-QUAL-ICM, QUAL2k) are valuable and widely used management tools for algal accrual due to excess nutrients in the presence of other limiting factors. These models utilize the Monod and Droop equations to associate algal growth rate with dissolved nutrient concentration and intra-cellular nutrient content. Having accurate parameter values is essential to model performance, however published values for model parameterization are limited, particularly for benthic (periphyton) algae. We conducted a 10-day mesocosm experiment and measured diatom-dominated periphyton biomass accrual through time as chlorophyll a (chl a) and ash-free dry mass (AFDM) in response to additions of N (range 5-11,995 µg NO3-N/L) and P (range 0.89-59.51 µg SRP/L). Resulting half saturation coefficients and growth rates are similar to other published values, but minimum nutrient quotas are higher than those previously reported. Saturation concentration for N ranged from 150 to 2450 µg NO3-N/L based on chl a and from 8.5 to 60 µg NO3-N/L when based on AFDM. Similarly, the saturation concentration for P ranged from 12 to 29 µg-P/L based on chl a, and from 2.5 to 6.1 µg-P/L based on AFDM. These saturation concentrations provide an upper limit for streams where diatom growth can be expected to respond to nutrient levels and a benchmark for reducing nutrient concentrations to a point where benthic algal growth will be limited.

Understanding the captivity effect on invertebrate communities transplanted into an experimental stream laboratory.

Little is known about how design and testing methodologies affect the macroinvertebrate communities that are held captive in mesocosms. To address this knowledge gap, we conducted a 32-d test to determine how seeded invertebrate communities changed once removed from the natural stream and introduced to the laboratory. We evaluated larvae survival and adult emergence in controls from 4 subsequent studies, as well as corresponding within-river community changes. The experimental streams maintained about 80% of the invertebrates that originally colonized the introduced substrates. Many macroinvertebrate populations experienced changes in numbers through time, suggesting that these taxa are unlikely to maintain static populations throughout studies. For example, some taxa (Tanytarsini, Simuliidae, Cinygmula sp.) increased in number, grew (Simuliidae), and possibly recruited new individuals (Baetidae) as larvae, while several also completed other life history events (pupation and emergence) during the 30- to 32-d studies. Midges and mayflies dominated emergence, further supporting the idea that conditions are conducive for many taxa to complete their life cycles while held captive in the experimental streams. However, plecopterans were sensitive to temperature changes >2 °C between river and laboratory. Thus, this experimental stream testing approach can support diverse larval macroinvertebrate communities for durations consistent with some chronic criterion development and life cycle assessments (i.e., 30 d). The changes in communities held captive in the experimental streams were mostly consistent with the parallel changes observed from in situ river samples, indicating that mesocosm results are reasonably representative of real river insect communities. Environ Toxicol Chem 2018;37:2820-2834. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Weed presence altered biotic stress and light signaling in maize even when weeds were removed early in the critical weed-free period.

Weed presence early in the life cycle of maize (typically, from emergence through the 8 to 12 leaf growth stage) can reduce crop growth and yield and is known as the critical weed-free period (CWFP). Even if weeds are removed during or just after the CWFP, crop growth and yield often are not recoverable. We compared transcriptome responses of field-grown hybrid maize at V8 in two consecutive years among plants grown under weed-free and two weed-stressed conditions (weeds removed at V4 or present through V8) using RNAseq analysis techniques. Compared with weed-free plant responses, physiological differences at V8 were identified in all weed-stressed plants and were most often associated with altered photosynthetic processes, hormone signaling, nitrogen use and transport, and biotic stress responses. Even when weeds were removed at V4 and tissues sampled at V8, carbon: nitrogen supply imbalance, salicylic acid signals, and growth responses differed between the weed-stressed and weed-free plants. These underlying processes and a small number of developmentally important genes are potential targets for decreasing the maize response to weed pressure. Expression differences of several novel, long noncoding RNAs resulting from exposure of maize to weeds during the CWFP were also observed and could open new avenues for investigation into the function of these transcription units.

Piloting a Coping Skills Group Intervention to Reduce Depression and Anxiety Symptoms in Patients Awaiting Kidney or Liver Transplant.

The authors evaluated the use of a coping skills group (CSG) therapy intervention to decrease depression and anxiety and increase healthy coping skills in a population of kidney and liver transplant candidates. The study, using a pre-posttest design, piloted a CSG with a convenience sample of 41 consenting participants on a waiting list or in workup for kidney or liver transplant. Two transplant social workers led five eight-week closed psychoeducational groups. Coping skills, depression symptoms, and anxiety symptoms were assessed preintervention, postintervention, and at follow-up one month later. Results suggest that the CSG group created significant changes in some coping areas, such as decreasing the use of denial and self-blame and increasing the use of acceptance, religion, and instrumental supports. In this study, instrumental supports are strategies such as seeking assistance, finding information, or asking for advice about what to do. The effects on instrumental supports did not sustain at the one-month follow-up. Anxiety and depression scores were significantly reduced, and these changes were sustained at one-month follow-up. This study supports the use of a group-based psychosocial intervention for the pretransplant population and will be most relevant to social workers practicing in the transplant field.

General surgery residency interviews: are we following best practices?

BACKGROUND: The interview is one of the most important factors in selecting candidates for general surgery residency. There is significant research on best practices for conducting interviews. Blinded interviews and standardized questions improve interview utility and accuracy; however, their utilization in surgical residency programs is unclear. The purpose of this study was to determine the current practices of surgery residency programs in the interview process and the application of established best practices. METHODS: An online survey consisting of 26 questions was distributed to program directors of accredited surgery residency programs in the United States and Canada. RESULTS: Overall, 108 responses (40%) were received. The vast majority of programs (90%) reported basing at least 25% of their final ranking on the interview score. Only 22 (20%) programs reported using some form of blinding for their interviewers. Five programs (5%) reported using standardized interview questions. CONCLUSIONS: Few residency programs use blinded interviews or standardized questions. This may indicate a gap between research findings and practice and may represent an area for improvement in the resident selection process.

Tillage and corn residue harvesting impact surface and subsurface carbon sequestration.

Corn stover harvesting is a common practice in the western U.S. Corn Belt. This 5-yr study used isotopic source tracking to quantify the influence of two tillage systems, two corn ( L.) surface residue removal rates, and two yield zones on soil organic C (SOC) gains and losses at three soil depths. Soil samples collected in 2008 and 2012 were used to determine C enrichment during SOC mineralization, the amount of initial SOC mineralized (SOC), and plant C retained in the soil (PCR) and sequestered C (PCR - SOC). The 30% residue soil cover after planting was achieved by the no-till and residue returned treatments and was not achieved by the chisel plow, residue removed treatment. In the 0- to 15-cm soil depth, the high yield zone had lower SOC (1.49 Mg ha) than the moderate yield zone (2.18 Mg ha), whereas in the 15- to 30-cm soil depth, SOC was higher in the 60% (1.38 Mg ha) than the 0% (0.82 Mg ha) residue removal treatment. When the 0- to 15- and 15- to 30-cm soil depths were combined, (i) 0.91 and 3.62 Mg SOC ha were sequestered in the 60 and 0% residue removal treatments; (ii) 2.51 and 0.36 Mg SOC ha were sequestered in the no-till and chisel plow treatments, and (iii) 1.16 and 1.65 Mg SOC ha were sequestered in the moderate and high yield zone treatments, respectively. The surface treatments influenced C cycling in the 0- to 15- and 15- to 30-cm depths but did not influence SOC turnover in the 30- to 60-cm depth.

RNAseq reveals weed-induced PIF3-like as a candidate target to manipulate weed stress response in soybean.

Weeds reduce yield in soybeans (Glycine max) through incompletely defined mechanisms. The effects of weeds on the soybean transcriptome were evaluated in field conditions during four separate growing seasons. RNASeq data were collected from six biological samples of soybeans growing with or without weeds. Weed species and the methods to maintain weed-free controls varied between years to mitigate treatment effects, and to allow detection of general soybean weed responses. Soybean plants were not visibly nutrient- or water-stressed. We identified 55 consistently downregulated genes in weedy plots. Many of the downregulated genes were heat shock genes. Fourteen genes were consistently upregulated. Several transcription factors including a PHYTOCHROME INTERACTING FACTOR 3-like gene (PIF3) were included among the upregulated genes. Gene set enrichment analysis indicated roles for increased oxidative stress and jasmonic acid signaling responses during weed stress. The relationship of this weed-induced PIF3 gene to genes involved in shade avoidance responses in Arabidopsis provide evidence that this gene may be important in the response of soybean to weeds. These results suggest that the weed-induced PIF3 gene will be a target for manipulating weed tolerance in soybean.

Prenatal and perinatal risk factors in a twin study of autism spectrum disorders.

INTRODUCTION: Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently. METHODS: Data from medical records and parent response questionnaires from 194 twin pairs, in which at least one twin had an ASD, were analyzed. RESULTS: Shared factors including parental age, prenatal use of medications, uterine bleeding, and prematurity did not increase concordance risks for ASDs in twins. Among the individual factors, respiratory distress demonstrated the strongest association with increased risk for ASDs in the group as a whole (OR 2.11, 95% CI 1.27-3.51). Furthermore, respiratory distress (OR 2.29, 95% CI 1.12-4.67) and other markers of hypoxia (OR 1.99, 95% CI 1.04-3.80) were associated with increased risks for ASDs in males, while jaundice was associated with an increased risk for ASDs in females (OR 2.94, 95% CI 1.28-6.74). CONCLUSIONS: Perinatal factors associated with respiratory distress and other markers of hypoxia appear to increase risk for autism in a subgroup of twins. Future studies examining potential gender differences and additional prenatal, perinatal and postnatal environmental factors are required for elucidating the etiology of ASDs and suggesting new methods for treatment and prevention.

Overexpression of eukaryotic initiation factor 4E is correlated with increased risk for systemic dissemination in node-positive breast cancer patients.

BACKGROUND: Molecular events impact systemic dissemination. Overexpression of eukaryotic initiation factor 4E (eIF4E) has been shown to predict worse clinical outcomes in breast cancer. Node-positive breast cancer patients were specifically studied to determine if eIF4E elevation increases risk for systemic dissemination. STUDY DESIGN: Two hundred two node-positive breast cancer patients were prospectively accrued and treated with standardized treatment and surveillance protocol. Tumor eIF4E protein level was quantified by Western blots as x-fold over benign samples from noncancer patients. Primary end point was systemic metastasis. RESULTS: Systemic recurrence was detected in 22.2% of the low eIF4E group, 27.3% of the intermediate group, and 49% of the high group, at a median follow-up of 47 months. A greater risk for systemic metastasis was seen in the high eIF4E group compared with the low group (log-rank test, p = 0.0084). Patients in the high eIF4E group had a 1.5-fold (hazard ratio = 1.52; 95% CI, 1.07-2.17; p = 0.0206) higher risk for systemic metastasis than the low group. Sixty percent of the patients with high eIF4E were observed to have metastasis to multiple sites, compared with 50% in the intermediate group, and 14.5% in the low group (p = 0.02, Fisher's exact test). When patients were segregated based on nodal classification (N1, N2, and N3), eIF4E overexpression continued to be a predictor for systemic dissemination in patients with N1 disease. CONCLUSIONS: High eIF4E is correlated with an increased risk for systemic metastasis in node-positive breast cancer patients. High eIF4E overexpression was associated with a higher incidence of metastasis to multiple sites. Therefore, high eIF4E overexpression appears to be a marker for molecular events that increases risk for systemic dissemination.

Head circumferences in twins with and without Autism Spectrum Disorders.

To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20 % of males and 27 % of females with an ASD had macrocephaly. Unaffected co-twins showed similar rates (16 % of males and 22 % of females). Statistical analysis revealed no significant difference in HCs between affected and unaffected twins. Twins with ASDs and unaffected co-twins have similar HCs and increased rates of macrocephaly. Correlations demonstrated partial inheritance of HCs. Thus, macrocephaly may represent an endophenotype in ASDs.

Genetic heritability and shared environmental factors among twin pairs with autism.

CONTEXT: Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins. OBJECTIVE: To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. DESIGN, SETTING, AND PARTICIPANTS: Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services. MAIN OUTCOME MEASURES: Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD). RESULTS: For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD). CONCLUSION: Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.

Globalization of P4 medicine: predictive, personalized, preemptive, and participatory--summary of the proceedings of the Eighth International Symposium of the International Society for Strategic Studies in Radiology, August 27-29, 2009.

In August 2009, the International Society for Strategic Studies in Radiology held its eighth biennial meeting. The program focused on the globalization of predictive medicine--or P4 medicine--as it relates to the practice of radiology and radiology research. P4 medicine refers to predictive, personalized, preemptive, and participatory medicine and was the inspiration of Elias Zerhouni, MD, former director of the National Institutes of Health. This article is a summary of some of the key concepts presented at the meeting by an international group of radiologists, imaging scientists, and leaders of industry. In predictive medicine, imaging and imaging-related technologies will likely play an increasing role in the early detection of disease and, thus, the preemption of the development of advanced, hard-to-treat disease. Research into systems biology and molecular imaging promises to personalize medicine, facilitating the provision of the right care to the right patient at the right time. In participatory medicine, increasing interactions with referring physicians and patients will be helpful in raising awareness and recognition of the role of radiologists and will have a positive effect on professionalism. There is also a need to increase awareness of the vital role of radiologists as imaging and radiation safety experts who evaluate the necessity and appropriateness of examinations, monitor performance quality, and are available for postexamination consultations.

Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus.

BACKGROUND: Reactive astrocytosis and microgliosis are important features of the pathophysiology of hydrocephalus, and persistent glial "scars" that form could exacerbate neuroinflammation, impair cerebral perfusion, impede neuronal regeneration, and alter biomechanical properties. The purpose of this study was to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce gliosis in the H-Tx rat model of congenital hydrocephalus. METHODS: Minocycline (45 mg/kg/day i.p. in 5% sucrose at a concentration of 5-10 mg/ml) was administered to hydrocephalic H-Tx rats from postnatal day 15 to day 21, when ventriculomegaly had reached moderate to severe stages. Treated animals were compared to age-matched non-hydrocephalic and untreated hydrocephalic littermates. The cerebral cortex (both gray matter laminae and white matter) was processed for immunohistochemistry (glial fibrillary acidic protein, GFAP, for astrocytes and ionized calcium binding adaptor molecule, Iba-1, for microglia) and analyzed by qualitative and quantitative light microscopy. RESULTS: The mean number of GFAP-immunoreactive astrocytes was significantly higher in untreated hydrocephalic animals compared to both types of controls (p < 0.001). Minocycline treatment of hydrocephalic animals reduced the number of GFAP immunoreactive cells significantly (p < 0.001). Likewise, the mean number of Iba-1 immunoreactive microglia was significantly higher in untreated hydrocephalic animals compared to both types of controls (p < 0.001). Furthermore, no differences in the numbers of GFAP-positive astrocytes or Iba-1-positive microglia were noted between control animals receiving no minocycline and control animals receiving minocycline, suggesting that minocycline does not produce an effect under non-injury conditions. Additionally, in six out of nine regions sampled, hydrocephalic animals that received minocycline injections had significantly thicker cortices when compared to their untreated hydrocephalic littermates. CONCLUSIONS: Overall, these data suggest that minocycline treatment is effective in reducing the gliosis that accompanies hydrocephalus, and thus may provide an added benefit when used as a supplement to ventricular shunting.