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Objectives: Objective of this study is to investigate whether there is any effect of accommodation on Autoref reading before and after cycloplegia and to check out which age and type of refractive error is more effected by accommodation. Methods: An informed consent was obtained describing the detail of study and its implication. Therefore the subject was assured of their confidentially of information and outcome. Four groups were selected and effect of accommodation on patients autoref reading were measured. Autorefractor reading was noted before and after cycloplegia. Autoref reading was taken without cycloplegia in different age groups and then by using cyclopentolate to relax the accommodation and by repeating the autoref reading to find out difference in reading before and after cycloplegia. 110 patients of age group 3 to 60 were assessed by that method. Results: Accommodation affects different age groups except old age. Accommodation effects on refractive error more in age 3-15 years because accommodation is stronger in children. There was significant difference between morning and evening amplitude of accommodation as p<0.005. Conclusions: Accommodation affects different age group and the effect is maximum between 3-15 years and decreases with increasing age. Autoref overestimate myopia and under estimate hyperopia without cycloplegia. By using cycloplegia exact refractive error can be measured. [ABSTRACT FROM AUTHOR]

Purpose: The key purpose of this study was to evaluate the proportion of dry eyes in patients of computer vision syndrome. Study Design: Descriptive cross sectional study. Material & Method: 100 students (55 males and 45 females) of King Edward Medical University, Lahore and HBS Medical and Dental College Hospital, Islamabad, having age group 18-30 years of both genders were included in the study. Data was composed using a structured proforma and 22 items questionnaire in all age groups having computer vision syndrome. Results: The schirmer test was performed to assess dry eyes in patients with computer vision syndrome. The results showed that 82% of patients with computer vision syndrome suffer from dry eyes as mean value on schirmer test was 9.52mm and 18% patients were normal with no dry eye symptom as the mean value on schirmer test was 15.44mm. The p-value (p=0.01) shows highly significant association between dry eye and computer vision syndrome. Conclusion: It is concluded that there is risk of dry eye patients among CVS as assessed by schirmer test. This risk increases with the duration of computer usage and elderly females are more prone to develop dry eye syndrome as compared to males. [ABSTRACT FROM AUTHOR]

• Synthesized heteroleptic organotin(IV) complexes showed potent anticancer activity. • Complex 5 exhibited pentagonal bipyramidal geometry via single crystal XRD analysis. • DNA binding studies revealed groove binding and dual interaction modes with SS-DNA. • Anticancer complexes induced S phase arrest and apoptosis via intrinsic pathways. Herein heteroleptic tri- and di-butylorganotin(IV) carboxylate complexes with general formula R 3 SnL(N-N´)/R 2 SnL 2 (N-N´) have been synthesized using 3-methylbenzoic acid (L) as primary ligand and N-N´ donor heterocycles namely 2,2′-bipyridine (1 and 4), 1, 10-phenanthroline (2 and 5) and 2,9-dimethyl-1,10-phenanthroline (3 and 6) as hetero-ligands. The as-synthesized complexes were characterized by multitude spectroscopic techniques. Among the synthesized complexes, the complex 5 crystallized in triclinic crystal system and the single crystal analysis revealed that Sn(IV) center is seven coordinated resulting in a pentagonal bipyramidal geometry. The DNA binding affinity of the synthesized complexes was evaluated through UV–Visible spectroscopy, viscometry and theoretically through molecular docking. The results demonstrated that complexes possess high potential to bind with DNA through a spontaneous process. The complexes were tested for anticancer activities and were found to be potent having IC 50 values comparable to standard drug Doxorubicin. Furthermore, potent complexes (2 and 6) caused an arrest in synthesis phase and activated intrinsic pathway of apoptosis in treated cancer cells. [ABSTRACT FROM AUTHOR]

Six new Schiff based diorganotin(IV) complexes have been synthesized and structurally characterized through multitude analytical techniques. The compound-DNA interaction study has been performed through UV–Visible spectroscopy that revealed high binding potential through a spontaneous process. The complexes have further been investigated for in vitro antimicrobial and anticancer studies. [Display omitted] • Synthesis of six diorganotin(IV) complexes based on two new Schiff base ligands derived by the condensation reaction of aldehydes with acid hydrazides. • Spectroscopic characterization and structural elucidation of all complexes were performed. • Compound-DNA interaction study was performed through UV–Visible spectroscopy. • The compounds were investigated for in vitro antimicrobial studies. • The compounds were evaluated for their anticancer activities. Herein, two Schiff base ligands Ń-(4-diethylamino-2-hydroxybenzylidene) isonicotinohydrazide (L1) and Ń-(2,3-dihydroxybenzylidene) isonicotinohydrazide (L2) and their six di-organotin(IV) complexes (R = C 4 H 9 (1 , 4), C 6 H 5 (2 , 5) and CH 3 (3 , 6)) were synthesized. The solid state and solution chemistry of the ligands and their organotin(IV) complexes was explored through single crystal XRD, FTIR and NMR (1H, 13C and 119Sn) spectroscopy. The single crystal XRD analysis was carried out for complexes 1 , 2 and 5 , reveals the presence square pyramidal, trigonal bipyramidal and pentagonal bipyramidal geometries, respectively. All structures showed distorted geometries because of the constraint offered by five and six membered chelate rings. The results obtained from the interaction study of ligands and complexes with SS-DNA were indicative of high binding potential through a spontaneous process. The results of in vitro antimicrobial studies validated the well-known theory of chelation and overtone concept. Anticancer activities conducted for the ligands and complexes revealed evident anti-proliferative activity of 1 , 2 , 4 and 5 complexes. Complex 2 being the most active one, exhibited pro-apoptotic, cytotoxic effect after PI and DAPI stains. Moreover, after H2DCF-DA staining the treated cancerous cells, an induced oxidative stress was detected. Complexes 2 and 4 also revealed the activation of mitochondrial pathway of apoptosis in treated cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Traumatic brain injury can cause extensive damage to the white matter (WM) of the brain. These disruptions can be especially damaging in children, whose brains are still maturing. Diffusion magnetic resonance imaging (dMRI) is the most commonly used method to assess WM organization, but it has limited resolution to differentiate causes of WM disruption. Magnetic resonance spectroscopy (MRS) yields spectra showing the levels of neurometabolites that can indicate neuronal/axonal health, inflammation, membrane proliferation/turnover, and other cellular processes that are on‐going post‐injury. Previous analyses on this dataset revealed a significant division within the msTBI patient group, based on interhemispheric transfer time (IHTT); one subgroup of patients (TBI‐normal) showed evidence of recovery over time, while the other showed continuing degeneration (TBI‐slow). We combined dMRI with MRS to better understand WM disruptions in children with moderate‐severe traumatic brain injury (msTBI). Tracts with poorer WM organization, as shown by lower FA and higher MD and RD, also showed lower N‐acetylaspartate (NAA), a marker of neuronal and axonal health and myelination. We did not find lower NAA in tracts with normal WM organization. Choline, a marker of inflammation, membrane turnover, or gliosis, did not show such associations. We further show that multi‐modal imaging can improve outcome prediction over a single modality, as well as over earlier cognitive function measures. Our results suggest that demyelination plays an important role in WM disruption post‐injury in a subgroup of msTBI children and indicate the utility of multi‐modal imaging. [ABSTRACT FROM AUTHOR]

ABSTRACT Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ 2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ 2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ 2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multicomponent reactions strategy has been used to 3,4-Dihydropyrimidin-2(1 H)-Ones. • The resulting N -Heterocyclic compounds have been evaluated for biological activity MAO A and B. • The library of 3,4-dihydropyrimidin-2(1 H)-ones has also been evaluated as cholinesterases inhibitors. • Molecular docking was also performed to study the interaction of compound with target enzymes. Substitution of hazardous and often harmful organic solvents with "green" and "sustainable" alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1 H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC 50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC 50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC 50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer., (© 2023. The Author(s).)

Background: Preoperative administration of oral antibiotic bowel preparation (OABP) alone has been shown to reduce infectious outcomes in patients undergoing elective colectomy. However, it remains unclear if these benefits extend to the emergency setting. This is a retrospective, propensity-score matched study comparing 30-day perioperative morbidity between those who received OABP alone versus no preparation prior to urgent colectomy., Methods: Using the American College of Surgeons National Surgical Quality Improvement Program database, adults undergoing urgent colectomy from 2012 to 2019 were included. Those who were clinically obstructed or who received mechanical bowel preparation were excluded. Outcomes of interest included: surgical site infection (SSI), leak, ileus, and major morbidity., Results: Of 24,559 patients meeting inclusion criteria, 878 (3.6%) received OABP prior to urgent colectomy. Prior to matching, those receiving no preparation were more likely to have higher ASA class, diabetes, hypertension, preoperative sepsis, open procedures, and a dirty wound classification. After matching, 1756 patients, remained with 878 in each arm. Preoperative characteristics were balanced on univariate analysis. Postoperatively, patients receiving OABP experienced decreased organ space SSI (11.2% vs. 15.5%, p = 0.009) and ileus (30.3% vs. 35.3%, p = 0.029), with no difference in leak rates (3.3% vs 3.3%, p = 1.000) or NSQIP major morbidity (47.4% vs. 49.9%, p = 0.316). On multivariate logistic regression, including propensity score, the reduction in organ space SSI associated with OABP persisted (OR 0.684, 95% CI 0.516-0.903)., Conclusion: OABP prior to select urgent colectomies was associated with fewer organ space SSIs and may be considered when feasible., (© 2022. The Society for Surgery of the Alimentary Tract.)

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase ( h -TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h -TNAP, having IC 50 values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h -TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure-activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h -TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.

Background: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA)., Methods: Neuroimaging and clinical data were aggregated from 29 research sites in >1300 PTSD cases and >2000 trauma-exposed control subjects (ages 6.2-85.2 years) by the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta Analysis-Psychiatric Genomics Consortium) PTSD working group. Cortical regions in the network were rank ordered by the effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2-148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared with the mean SC of 5000 randomly generated n-region networks., Results: Patients with PTSD, relative to non-PTSD control subjects, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex, and age modulated covariance differences of PTSD-related structural networks., Conclusions: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The SC networks that are perturbed in PTSD comport with converging evidence from resting-state functional connectivity networks and networks affected by inflammatory processes and stress hormones in PTSD., (Copyright © 2022 Society of Biological Psychiatry. All rights reserved.)

Introduction: Transanal total mesorectal excision (TaTME) is a novel procedure in the treatment of rectal cancer. Current training models for TaTME suggest a period of proctored cases, but no structured feedback tool exists to guide operators during the learning phase. The objective of this study therefore was to develop a formative feedback tool for the critical steps of the transanal portion of TaTME., Methods: A two-round Delphi study by TaTME experts was conducted to determine the items to be included in the formative feedback tool. Participants rated each step from a prepared list using a Likert scale from 1 (Not relevant) to 5 (Very relevant) with the option to suggest additional steps. Responses to the first round were presented in the second round, where participants rated the revised list of steps. Consensus was defined as > 80% of participants rating the step as 4 or 5 (out of 5). Items were combined when appropriate to avoid redundancy. Rating anchors describing performance (on a 5-point scale) were then developed for each step. The final tool was recirculated and participants rated the finished product on its feasibility and usefulness., Results: Twenty-six TaTME experts were contacted for participation. Fifteen experts (58%) participated in the first round of the study, and eleven (42%) participated in the second round. The majority (14, 93%) had completed fellowship training in colorectal surgery. The first round of the Delphi study contained 34 items, and 32 items met inclusion criteria after the second round. Redundant items were combined into 15 items that comprised the final tool. Out of eight respondents to the feasibility survey, all believed the feedback tool enhances the feedback of learners and would use it for training purposes if available., Conclusion: This work describes the development of a novel consensus-based formative feedback tool specific to TaTME., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: The objective of this study was to determine whether right-sided colectomies (RC) were associated with a higher incidence of primary postoperative ileus (pPOI) compared to left-sided colectomies (LC)., Methods: Patients who underwent elective colectomy for neoplastic disease between 2012 and 2016 were identified using the American College of Surgeons National Surgical Quality Improvement Program database. RC and LC were defined as having an ileocolic or colocolic/colorectal anastomosis, respectively. Coarsened Exact Matching (CEM) was used to balance the two groups (1:1) on important confounders. The association between type of colectomy and pPOI, defined as POI in the absence of intra-abdominal sepsis, was then assessed in a multiple logistic regression analysis of the matched data., Results: Of 40,636 patients who underwent a colectomy for neoplastic disease, 15,231 underwent a RC and 25,405 a LC. After CEM, 12,949 matched patients remained in each group, and all important confounders were well balanced. The incidence of pPOI was higher in the RC group (11.5% vs. 8.8%, p < 0.001). On multiple logistic regression, RC was associated with a 35% higher odds of developing pPOI compared to LC (OR 1.35, 95% CI 1.25-1.47). RC was also associated with increased risk for NSQIP-defined major morbidity (OR 1.10, 95% CI 1.01-1.20), 30-day readmission (OR 1.16, 95% CI 1.06-1.27), and increased length of stay (β = 0.16 days, 95% CI 0.11-0.22)., Conclusion: pPOI is more common after RC than LC. Future research should aim at better understanding the pathophysiology behind this increased risk and identifying interventions to mitigate pPOI in this population.

Purpose: Most myeloablative regimens before stem cell transplant involved total body irradiation (TBI). Pulmonary complications from TBI contribute to treatment-related mortality and toxicity. We report the rate of acute respiratory complications after TBI at our institution. In an exploratory analysis, we investigated differences in dosimetry between patients who did and did not experience respiratory complications., Methods and Materials: In this single institution retrospective study, 49 patients received TBI from 2016 to 2018 and had dosimetry data available for analysis. Patients were prescribed 1200 cGy to be delivered over 6 fractions. Lung doses were limited using custom lung blocks. Clinical lung complications (eg, coughing and shortness of breath) were reviewed for the hospitalization period during transplant, at 4 months after transplant, and at 1 year after transplant. Supplemental oxygen use during the hospitalization period was also reported. Median anterior-posterior diameter at the umbilicus, body mass index, and lung doses were compared between patients with and without respiratory complications using a Mann-Whitney U test., Results: During the hospitalization period, 14% (n = 7) of patients used supplemental oxygen administered by nasal canula and 16% (n = 8) experienced respiratory symptoms. At the 4-month follow-up, 16% (n = 8) of patients had documented respiratory symptoms. Respiratory symptoms were grade 1 to 2 except for one grade 3 attributed to infection during the hospitalization period and another grade 3 due to infection during the 4-month follow-up. At 1-year post-TBI, 4% (n = 2) of patients reported grade 1 to 2 chronic cough. Patients with respiratory complications at the 4-month follow-up had a larger umbilical anterior-posterior diameter (31.5 cm vs 26.5 cm, P = .01) and body mass index (34.5 kg/m 2 vs 29.7 kg/m 2 , P = .02) than patients without respiratory complication. Respiratory complications were not associated with higher lung doses., Conclusions: There was no respiratory-related mortality using the individualized planning technique described here. Acute and chronic respiratory complications were minor, with the most significant intervention requiring antibiotics for respiratory infection., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: The true incidence of, and risk factors for, readmission for treatment failure after nonoperative management of acute diverticulitis remain poorly understood., Objective: The purpose of this study was to describe the incidence and risk factors for readmission for treatment failure after nonoperative management of acute diverticulitis using a large national database., Design: This was a retrospective cohort study., Settings: A representative sample of admissions and discharges from hospitals in the United States captured in the National Readmissions Database were included., Patients: Adult patients (age ≥18 y) admitted with a primary diagnostic of colonic diverticulitis between 2010 and 2015 and who were managed nonoperatively and discharged from hospital alive were included., Interventions: Study intervention included nonoperative management, consisting of medical therapy with or without percutaneous drainage., Main Outcome Measures: Readmission for treatment failure (defined as a nonelective readmission for diverticulitis within 90 d of discharge), complicated treatment failure (defined as a treatment failure with complicated diverticulitis), and time-to-treatment failure were measured., Results: In total, 201,384 patients were included. The overall incidence of readmission for treatment failure was 6.6%. Treatment failure was significantly higher among patients with an index episode of acute complicated diverticulitis compared with acute uncomplicated diverticulitis (12.5% vs 5.7%; p < 0.001). The median time-to-readmission for treatment failure was 21.0 days (range, 20.4-21.6 d), and 85% of all readmissions occurred within 60 days of discharge. On multiple logistic regression, factors independently associated with readmission for treatment failure were an index admission of complicated diverticulitis (OR = 2.06 (95% CI, 1.97-2.16)), disposition on discharge (against medical advice: OR = 1.92 (95% CI, 1.66-2.20); home health care arrangements: OR = 1.24 (95% CI, 1.16-1.33)), and immunosuppression (OR = 1.42 (95% CI, 1.28-1.57)), among others. Risk factors for a complicated treatment failure were also described, after an index episode of complicated and uncomplicated diverticulitis., Limitations: The study was limited by residual confounding from missing covariates and its observational study design., Conclusions: The incidence of readmission for treatment failure after an episode of diverticulitis managed nonoperatively is 6.6%, and an index episode of complicated diverticulitis is the strongest risk factor for treatment failure. See Video Abstract at http://links.lww.com/DCR/B92. REINGRESO POR FRACASO DEL TRATAMIENTO DESPUÉS DEL TRATAMIENTO NO QUIRÚRGICO DE LA DIVERTICULITIS AGUDA: UN ANÁLISIS DE LA BASE DE DATOS DE REINGRESOS A NIVEL NACIONAL: La verdadera incidencia y los factores de riesgo para el reingreso por fracaso del tratamiento después de manejo no quirúrgico de la diverticulitis aguda siguen siendo mal definidos.Definir la incidencia y los factores de riesgo de reingreso por fracaso del tratamiento no quirúrgico de la diverticulitis aguda utilizando una base de datos nacional.Estudio de cohorte retrospectivo.Una muestra representativa de ingresos y egresos de hospitales en los Estados Unidos capturados en la base de datos nacional de reingresos hospitalarios.Pacientes adultos (≥18 años) ingresados con un diagnóstico primario de diverticulitis colónica entre 2010-2015, y que fueron tratados de forma no operativa y dados de alta del hospital vivos.Manejo no quirúrgico, que consiste en terapia médica con o sin drenaje percutáneo.Reingreso por fracaso del tratamiento (definido como un reingreso no electivo por diverticulitis dentro de los 90 días despues de ser dados de alta), fracaso del tratamiento complicado (definido como un fracaso del tratamiento con diverticulitis complicada) y el tiempo hasta el tratamiento en casos fracasaados.201.384 pacientes incluidos en total. La incidencia global de reingreso por fracaso del tratamiento fue del 6,6%. El fracaso del tratamiento fue significativamente mayor entre los pacientes con un episodio índice de diverticulitis aguda complicada en comparación con la diverticulitis aguda no complicada (12.5% vs. 5.7%, p <0.001). La mediana del tiempo hasta el reingreso por fracaso del tratamiento fue de 21.0 (20.4 - 21.6) días, y el 85% de todos los reingresos ocurrieron dentro de los 60 días posteriores a ser dados de alta. En la regresión logística múltiple, los factores asociados independientemente con el reingreso por fracaso del tratamiento fueron un índice de admisión de diverticulitis complicada (OR 2.06, IC 95% 1.97-2.16), disposición (de alta en contra del consejo médico: OR 1.92, IC 95% 1.66-2.2; atención médica domiciliaria: OR 1.24, IC 95% 1.16-1.33) e inmunosupresión (OR 1.42, IC 95% 1.28-1.57), entre otros. Los factores de riesgo para un fracaso del tratamiento complicado también se describieron, respectivamente, después de un episodio índice de diverticulitis complicada y no complicada.Covariables faltantes y diseño de estudio observacional.La incidencia de reingreso por fracaso del tratamiento después de un episodio de diverticulitis manejado de forma no operativa es del 6,6%, y un episodio índice de diverticulitis complicada es el factor de riesgo más fuerte para el fracaso del tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B92. (Traducción-Dr. Adrian E. Ortega).

Objective: To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period., Methods: We studied 21 children (16 M/5 F) with msTBI, assessed 2-5 months postinjury and again 13-19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure. At the first time point, half of the patients with TBI had significantly slower IHTT (TBI-slow-IHTT, n = 11) and half were in the normal range (TBI-normal-IHTT, n = 10)., Results: The TBI-normal-IHTT group did not differ significantly from healthy controls, either in WM organization in the chronic phase or in the longitudinal trajectory of WM organization between the 2 evaluations. In contrast, the WM organization of the TBI-slow-IHTT group was significantly lower than in healthy controls across a large portion of the WM. Longitudinal analyses showed that the TBI-slow-IHTT group experienced a progressive decline between the 2 evaluations in WM organization throughout the brain., Conclusions: We present preliminary evidence suggesting a potential biomarker that identifies a subset of patients with impaired callosal organization in the first months postinjury who subsequently experience widespread continuing and progressive degeneration in the first year postinjury., (© 2017 American Academy of Neurology.)

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2-5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2-5 months post injury. We investigated how this subgroup (TBI-slow, N  = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N  = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory.

The role of the cerebrovascular network and its acute response to TBI is poorly defined and emerging evidence suggests that cerebrovascular reactivity is altered. We explored how cortical vessels are physically altered following TBI using a newly developed technique, vessel painting. We tested our hypothesis that a focal moderate TBI results in global decrements to structural aspects of the vasculature. Rats (naïve, sham-operated, TBI) underwent a moderate controlled cortical impact. Animals underwent vessel painting perfusion to label the entire cortex at 1 day post TBI followed by whole brain axial and coronal images using a wide-field fluorescence microscope. Cortical vessel network characteristics were analyzed for classical angiographic features (junctions, lengths) wherein we observed significant global (both hemispheres) reductions in vessel junctions and vessel lengths of 33% and 22%, respectively. Biological complexity can be quantified using fractal geometric features where we observed that fractal measures were also reduced significantly by 33%, 16% and 13% for kurtosis, peak value frequency and skewness, respectively. Acutely after TBI there is a reduction in vascular network and vascular complexity that are exacerbated at the lesion site and provide structural evidence for the bilateral hemodynamic alterations that have been reported in patients after TBI.

Brain development is a protracted and dynamic process. Many studies have charted the trajectory of white matter development, but here we sought to map these effects in greater detail, based on a large set of fiber tracts automatically extracted from HARDI (high angular resolution diffusion imaging) at 4 tesla. We used autoMATE (automated multi-atlas tract extraction) to extract diffusivity measures along 18 of the brain's major fiber bundles in 667 young adults, aged 18-30. We examined linear and non-linear age effects on diffusivity measures, pointwise along tracts. All diffusivity measures showed both linear and non-linear age effects. Tracts with the most pronounced age effects were those that connected the temporal lobe to the rest of the brain. Nonlinear age effects were picked up strongly in the anterior corpus callosum and right temporo-parietal tracts.

Traumatic brain injury (TBI) is the leading cause of death and disability in children, and can lead to long lasting functional impairment. Many factors influence outcome, but imaging studies examining effects of individual variables are limited by sample size. Roughly 20-40% of hospitalized TBI patients experience seizures, but not all of these patients go on to develop a recurrent seizure disorder. Here we examined differences in structural network connectivity in pediatric patients who had sustained a moderate-severe TBI (msTBI). We compared those who experienced early post-traumatic seizures to those who did not; we found network differences months after seizure activity stopped. We also examined correlations between network measures and a common measure of injury severity, the Glasgow Coma Scale (GCS). The global GCS score did not have a detectable relationship to brain integrity, but sub-scores of the GCS (eyes, motor, verbal) were more closely related to imaging measures.

Traumatic brain injury (TBI) can disrupt the white matter (WM) integrity in the brain, leading to functional and cognitive disruptions that may persist for years. There is considerable heterogeneity within the patient group, which complicates group analyses. Here we present improvements to a tract identification workflow, automated multi-atlas tract extraction (autoMATE), evaluating the effects of improved registration. Use of study-specific template improved group classification accuracy over the standard workflow. The addition of a multi-modal registration that includes information from diffusion weighted imaging (DWI), T 1 -weighted, and Fluid-Attenuated Inversion Recovery (FLAIR) further improved classification accuracy. We also examined whether particular tracts contribute more to group classification than others. Parts of the corpus callosum contributed most, and there were unexpected asymmetries between bilateral tracts.

Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsy-predictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy.