First Report of Blight Caused by Rhizoctonia solani AG4-HGI on Pinellia ternata in Guizhou, China.

Pinellia ternata (Thumb.) has been used for over 1000 years as a traditional Chinese herbal medicine (Ying et al. 2007) and is widely cultivated in Guizhou Province, China. It is cultivated over an area of 2000 hectares, and is of great value to underdeveloped regions. In April 2020, blight was observed in a field of P. ternatain Bijie County, Guizhou Province, China (27°30'N, 105°28'E). Around 20 hectares of P. ternata were surveyed and the disease incidence ranged from 10 to 12%. The disease symptoms included light brown lesions formed on the stems near the soil line. The color of the lesions became darker, and the stems became constricted around the lesions and broke, associated with the leaf blight. To identify the causal agent of this blight, 22 diseased plants (about 30 d-old） were collected, the margins of the infected parts were cut into small pieces (5 mm) and surface disinfested with 1% NaOCl for 10 min, 75% ethanol for 30 s, and rinsed three times in sterile distilled water. The pieces were blotted dry with sterile filter paper and placed on potato dextrose agar (PDA, Hopebio, China), incubated at 28℃ in darkness until fungal hyphae growth was visible. Sixteen cultures with different morphologies were recovered from the samples. When representative isolates of each culture type were inoculated onto plants, one produced similar blight symptoms. The representative isolate was called CD-1. The colony color was first white but turned light brown after grown on PDA for 6-7 d, and produced dark brown sclerotia. The hyphae were branched at right angles, with a slight constriction at the base of the branches and a septum near the junction where the branch separates from the main hyphae. Hyphal cells were stained with 0.5% Safranin O and 3% KOH and were observed to be multinucleate. These morphological features indicated that CD-1 likely is R. solani (Sneh et al. 1991). When paired with tester strains AG1 and AG4(provided by Dr. Genhua Yang, Yunnan Agricultural University). CD-1 showed anastomosis with isolate of AG4 (Fenille et al. 2002). Genomic DNA was extracted from the isolate (Thangaraj et al. 2018) using a fungal genomic DNA extraction kit (Tiangen, China). The internal transcribed spacer (ITS) regions were amplified using the primers ITS1/ITS4 (White et al. 1990). A 535 bp fragment was amplified that showed 99% coverage and 99.4% identity with an isolate of R. solani AG4-HGI (GenBank: HG934417). The gene sequence was deposited in GenBank as accession #OL518945. Pathogenicity tests were performed using 30 d-old plants planted in sterilized soil in pots. Cut mycelial discs (diameter 6 mm) from 3-day-old PDA cultures and placed beside stems of 21 healthy plants. Nine plants treated with agar plugs were control samples. Inoculated plants were maintained at 24 ± 5℃ in a green house and watered every two days with sterilized water. Typical blight symptoms developed on the inoculated plants at d 3-5 post inoculation, whereas the control plants remained healthy. The experiments were repeated three times, and the isolates was re-isolated from the inoculated plants and identified as R. solaniAG4 by morphological features and molecular method. R. solani has been reported to cause blight of many plants such as coffee (Ren et al. 2018) and sesame (Cochran et al. 2018). To the best of our knowledge, this is the first report of R. solani AG4-HGI causing disease on P. ternate, both in China and worldwide. This finding suggests that this pathogen may cause a threat to cultivation and production of P. terenata.

Facial Fractures: Independent Prediction of Neurosurgical Intervention.

Context Over half of patients with facial fractures have associated traumatic brain injury (TBI). Based on force dynamic cadaveric studies, Le Fort type 2 and 3 fractures are associated with severe injury. Correlation to neurosurgical intervention is not well characterized. Aims This study characterizes fracture pattern types in patients requiring neurosurgical intervention and assesses whether this is different from those not requiring intervention. Settings and Design Retrospective data was collected from the trauma registry from 2010 to 2019. Methods and Materials Patients over 18 years, with confirmed facial fracture, reported TBI, available neuroimaging, and hospital admission were included. Statistical Analysis Retrospective contingency analysis with fraction of total comparison was used with chi-square analysis for demographic and injury characteristic data. Results Note that 1,001 patients required no neurosurgical intervention and 171 required intervention. The intervention group had a significantly greater number of patients with Glasgow Coma Scale (GCS) < 8 compared with the nonintervention group. Subset analysis revealed a twofold increase in Le Fort type 2 fractures and notable increase in Le Fort type 3 and panfacial fractures in the intervention group. Patients requiring craniectomy, craniotomy, or burr holes were much more likely to have Le Fort type 2 or 3 fractures compared with those only requiring external ventricular drains or intracranial pressure monitoring. Subset analysis accounting for GCS supported these results. Conclusion Le Fort type 2 and type 3 fractures are significantly associated with requiring neurosurgical intervention. An improved algorithm for managing these patients has been proposed in the discussion. Ongoing work will focus on validating and refining the algorithm to improve patient care.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Prevention and Attenuation of COVID-19 by BNT162b2 and mRNA-1273 Vaccines

BACKGROUNDInformation is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions. METHODSProspective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020--April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). VE was calculated as 100%x(1-hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation. RESULTSSARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially ([≥]14 days post-dose-1 to 13 days after dose-2) or fully ([≥]14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%-97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants. CONCLUSIONSAuthorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.

A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes' interactions points to Neutrophil extracellular traps as mediators of thrombosis in COVID-19.

Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders.

Facial Fractures: Independent Prediction of Neurosurgical Intervention.

CONTEXT: Over half of patients with facial fractures have associated traumatic brain injury (TBI). Based on force dynamic cadaveric studies, Lefort type 2 and 3 fractures are associated with severe injury. Correlation to neurosurgical intervention is not well characterized. AIMS: This study characterizes fracture pattern types in patients requiring neurosurgical intervention and assesses whether this is different from those not requiring intervention. SETTINGS AND DESIGN: Retrospective data were collected from the trauma registry from 2010 to 2019. SUBJECTS AND METHODS: Patients over 18, with confirmed facial fracture, reported TBI, available neuroimaging, and hospital admission were included. STATISTICAL ANALYSIS USED: Retrospective Contingency Analysis with Fraction of Total Comparison was used with Chi-square analysis for demographic and injury characteristic data. RESULTS: One thousand and one patients required no neurosurgical intervention and 171 required intervention. The intervention group had a significantly greater number of patients with Glasgow Coma Scale (GCS) <8 compared to the nonintervention group. Subset analysis revealed a twofold increase in Lefort type 2 fractures and notable increase in Lefort type 3 and panfacial fractures in the intervention group. Patients requiring craniectomy, craniotomy, or burr holes were much more likely to have Lefort type 2 or 3 fractures compared to those only requiring external ventricular drains or intracranial pressure monitoring. Subset analysis accounting for GCS supported these results. CONCLUSIONS: Lefort type 2 and type 3 fractures are significantly associated with requiring neurosurgical intervention. An improved algorithm for managing these patients has been proposed in the discussion. Ongoing work will focus on validating and refining the algorithm to improve patient care.

Phenotypic and Transcriptomic Analysis of Two Pinellia ternata Varieties T2 line and T2Plus line.

Pinellia (Pinellia ternata (Thunb.) Breit.), as important medicinal plant, has been used to treat various ailments for a long time. The sixteen ploid plant (2n = 16 * 13 = 208) Pinellia T2Plus line was obtained from an octoploid (2n = 8 * 13 = 104) T2 line by chromosome-doubling technique. Compared with T2 line, the content of various medicinal components (polysaccharide, guanosine, adenosine and ephedrine) was increased in T2Plus line. In this study, the transcriptome of T2 line and T2Plus line were characterized by RNA sequencing (RNA-seq) technology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis on differential expressed unigenes (DEGs) revealed that multiple metabolic pathway were enriched significantly, such as 'Starch and sucrose metabolism', 'Purine metabolism', 'Photosynthesis' and six transcription factors (MYB, WRKY, bHLH, lateral organ boundaries domain (LBD), homeodomain-zipper (HD-ZIP) and Ethylene-responsive factor (ERF)) play a key role in difference of transcriptome between T2 line and T2Plus line. These metabolic pathways and transcription factors may play an important role in the difference of medicinal components and epigenetic features between these two Pinellia cultivars. This conclusion provides a robust theoretical basis for the mechanism of the formation of medicinal ingredients in Pinellia cultivars.

Traps and trumps from adjacent-to-tumor samples in gastric cancer research.

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opportunities to the discovery of cancer biomarkers and molecular targets.

GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.

The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.

The role of piRNA and its potential clinical implications in cancer.

Epigenetic mechanisms work in an orchestrated fashion to control gene expression in both homeostasis and diseases. Among small noncoding RNAs, piRNAs seem to meet the necessary requirements to be included in this epigenetic network due to their role in both transcriptional and post-transcriptional regulation. piRNAs and PIWI proteins might play important roles in cancer occurrence, prognosis and treatment as reported previously. Nevertheless, the potential clinical relevance of these molecules has yet been elucidated. A brief overview of piRNA biogenesis and their potential roles as part of an epigenetic network that is possibly involved in cancer is provided. Moreover, potential strategies based on the use of piRNAs and PIWI proteins as diagnostic and prognostic biomarkers as well as for cancer therapeutics are discussed.

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice.

Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid ß peptide (Aß) within walls of cerebral arteries and is an important cause of intracerebral hemorrhage, ischemic stroke, and cognitive dysfunction in elderly patients with and without Alzheimer's Disease (AD). NADPH oxidase-derived oxidative stress plays a key role in soluble Aß-induced vessel dysfunction, but the mechanisms by which insoluble Aß in the form of CAA causes cerebrovascular (CV) dysfunction are not clear. Here, we demonstrate evidence that reactive oxygen species (ROS) and, in particular, NADPH oxidase-derived ROS are a key mediator of CAA-induced CV deficits. First, the NADPH oxidase inhibitor, apocynin, and the nonspecific ROS scavenger, tempol, are shown to reduce oxidative stress and improve CV reactivity in aged Tg2576 mice. Second, the observed improvement in CV function is attributed both to a reduction in CAA formation and a decrease in CAA-induced vasomotor impairment. Third, anti-ROS therapy attenuates CAA-related microhemorrhage. A potential mechanism by which ROS contribute to CAA pathogenesis is also identified because apocynin substantially reduces expression levels of ApoE-a factor known to promote CAA formation. In total, these data indicate that ROS are a key contributor to CAA formation, CAA-induced vessel dysfunction, and CAA-related microhemorrhage. Thus, ROS and, in particular, NADPH oxidase-derived ROS are a promising therapeutic target for patients with CAA and AD.

Prevalence and impact of subclinical thyroid dysfunction on mortality among patients presenting with cardiovascular events / Journal of the ASEAN Federation of Endocrine Societies

Objective@#This study aims to determine the prevalence of subclinical thyroid dysfunction among cardiac patients at the Philippine General Hospital, and its association with mortality. @*Methodology@#163 adult cardiac patients were screened for subclinical thyroid dysfunction, [subclinical hyperthyroidism (SCT), subclinical hypothyroidism (SCHO), non-thyroidal illness syndrome (NTIS)]. Demographic and clinical characteristics were analyzed using ANOVA and Fisher’s exact test. Outcome considered were hospital duration, need for mechanical ventilation, inotropic support and mortality. Crude association between subclinical thyroid dysfunction and outcomes was evaluated using relative risk. @*Results@#Prevalence of subclinical thyroid dysfunction was 32.5% (5.5% SCT, 5.5% SCHO, and 21.5% NTIS). The risk of necessitating mechanical ventilation was about twofold higher in subclinical thyroid dysfunction compared to euthyroid patients (RR=2.64), and was highest in SCHO (RR=3.71). The risk of inotropic support was about twofold higher (RR=2.70) in SCHO compared to euthyroid patients. Overall death rate was higher in subclinical thyroid dysfunction (RR=1.86), and highest in SCHO (RR=2.47) compared to euthyroid patients. @*Conclusion@#There is a significant prevalence of subclinical thyroid dysfunction among hospitalized patients with cardiac disease at 32.5%. Cardiovascular risk factors are not statistically significant. We observed a trend of increased risk of requiring mechanical ventilation, inotropes and overall mortality in SCHO.

Phosphodiesterase 5 inhibition attenuates cerebral vasospasm and improves functional recovery after experimental subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5), an enzyme that degrades cGMP, may play a role because the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered. OBJECTIVE: To elucidate the mechanism of action of sildenafil against vasospasm and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses. METHODS: SAH was induced via endovascular perforation in male C57BL6 mice. Beginning 2 hours later, mice received sildenafil citrate (0.7, 2 or 5 mg/kg orally twice daily) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure, and intracranial pressure were examined. RESULTS: We found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to decrease vasospasm and neuronal cell death and markedly improve neurological outcome without causing significant physiological side effects. CONCLUSION: Sildenafil, a US Food and Drug Administration-approved drug with a proven track record of safety in humans, is a promising new therapy for vasospasm and neurological deficits after SAH.

Knowledge, attitudes and practices of persons with type 2 diabetes in a rural community: phase I of the community-based Diabetes Self-Management Education (DSME) Program in San Juan, Batangas, Philippines.

AIMS: 1. To determine the knowledge, attitudes, and practices of persons with type 2 diabetes in the rural community of San Juan, Batangas, Philippines. 2. To determine the association between patient factors such as age, sex, duration of diabetes, and type of diabetes on knowledge, attitudes, and practices regarding diabetes. METHODS: Cross-sectional analytic study done among persons with type 2 diabetes in the rural community. Participants were selected using stratified cluster sampling. Data were collected using two main methods: use of investigator-administered questionnaires and focus group discussions (FGDs). RESULTS: 156 diabetic residents were included. The overall mean percentage score on knowledge was 43%. Less than half of the respondents strongly believed in the need for patient autonomy (38%). 35 respondents were included in the FGDs. Only 4 out of 35 diabetic respondents owned a glucose meter while only 16 out of the 35 consult their doctors on a regular basis. CONCLUSIONS: The study comprises Phase I of the proposed 5-year community-based DSME Program in the Philippines. It highlights the importance of evaluating knowledge, attitudes and practices as crucial means to understand observed behaviors and guide behavioral change.

Severe osteoporosis secondary to idiopathic hypogonadotrophic hypgonadism (IHH) in a 45-year old male

SYNOPSIS: Male hypogonadi sm i s an impor tant and treatable cause of osteoporosis. Severe osteoporosis leading to multiple osteoporotic fractures from idiopathic hypogonadotrophic hypogonadism (IHH) is rare. The present case illustrates the significance of timely and thorough evaluation of young adult males presenting with a seemingly ordinary complaint of "bone pains."THE CASE: I report a case of a 45 year-old male presenting with a 6-year history of progressive bone pains. Most prominent laboratory findings include low total serum tes tos terone (4.6 nmol/L) in the background of an inappropriately normal serum FSH, LH and sex hormonebinding globulin (SHBG). There is associated elevated urinary N- telopeptide (4x). Sperm analysis showed oligospermia. Scrotal ultrasound revealed normal-sized descended testis with no solid masses. Skeletal survey showed generalized decrease in bone density. Dual energy x-ray absortiometry (DXA) showed severe osteoporosis. Cranial CT scan with contrast did not show a sellar-suprasellar mass.TREATMENT AND OUTCOME: The patient was diagnosed with severe osteoporosis secondary to IHH. The patient received zoledronic acid (Aclasta) 5mg IV infusion. Two months after discharge, the patient reports a significant decrease in bone pains leading to more mobility. He is scheduled for his first dose of a GnRH agonist (Leuprodin acetate 3.75mg IM) to induce testosterone production.DISCUSSIONS: The incidence of osteoporosis among males is indirectly correlated to the reduction in circulating testosterone. First - line t reatment of os teoporosis in hypogonadal men is with bisphosphonates. Bisphosphanate therapy increase BMD, reduces vertebral fracture risk and is currently considered the standard of care for osteoporotic care for men.CONCLUSION: Osteoporosis is fast becoming a common condition among males. Osteoporotic fractures are associated with substantial morbidity and mortality. The present case emphasizes the importance of thorough and timely evaluation among men with low BMD or low-trauma fractures, which should include laboratory assessment to exclude secondary causes such as hypogonadism.

Trabecular organization in mandibular osteodistraction in growing and maturing rats.

PURPOSE: Our goal was to investigate the trabecular organization of the distraction regenerate during various consolidation phases and as a result of various distraction rates. MATERIALS AND METHODS: One hundred ninety-two growing and maturing rats (96 each) received unilateral mandibular osteotomies and distraction device placement. They were randomly allocated into 4 distraction rate groups (0, 0.2, 0.4, and 0.6 mm/day for 5 days) after a 3-day latency. Eight rats from each rate group were sacrificed at early (10 days), mid (24 days) and late (38 days) consolidation time points. Harvested hemimandibles were embedded in micro-bed resin, sectioned sagittally at 10 mum thickness and stained using the Von Kossa method. The histologic images were captured and processed using Adobe Photoshop (Version 7.0; Adobe Systems Inc, San Jose, CA). Custom-made software (MacAzimuth; written by Prof. J.M. Rensberger, University of Washington) was further used to analyze the orientation (anisotropy and angle distribution) and mass (density and thickness) of trabecular structures in the regenerates. RESULTS: Trabecular orientation significantly differed at the mid-consolidation time point with less anisotropy ( P < or = .000 to .023) and narrower angular distribution ( P < or = .007 to .021). Trabecular mass increased significantly from early to mid-consolidation ( P < or = .000 to .002). Growing rats showed greater trabecular organization than maturing rats did at the same time points ( P < or = .000 to .009). The trabecular organization parameters were associated significantly with bone mineral density and microdensity ( P < or = .000 to .044). CONCLUSION: The peak change in orientation occurred around the mid-consolidation with a greater increase in trabecular mass. Growing rats showed a greater capacity for trabecular organization at earlier time points. However, distraction rate did not have an effect on trabecular organization. These results suggest that trabecular organization can be used as an important indicator to evaluate bone maturation and quality in the distraction regenerate.