Validation of social cognition and interaction training's (SCIT) videos and photographs in Indian setting.

Background: Social cognition deficit is one of the marked characteristics of schizophrenia. Accumulated evidence suggests that social cognition and interaction training (SCIT) is associated with improved performance in social cognition and social skills in patients diagnosed with psychotic disorders. The cultural influence on social cognition is quite considerable. So, studies in the area of social cognition domains need to adapt and use culturally appropriate tools and measures to see the effectiveness. This study aimed to validate the materials used in SCIT training in Indian setting. Materials and Methods: The original script of video clips was translated into Hindi and was reshot, and the images were remade. A panel of experts rated the videos and images on a 5-point Likert scale. Furthermore, the content validity and internal consistency of the materials were calculated. Results: The content validity ratio (CVR) critical value was 0.357, and all the videos and images received more than the CVR critical value. The intraclass correlation coefficient for videos was 0.974, for SCIT photographs was 0.971, for "spotting character" was 0.975, and for "emotion shaping" was 0.965, indicating good internal consistency. Discussion: The majority of the experts in the panel found the videos and images adequate and appropriate for the Indian setting. In addition, the videos and photographs both yielded good internal consistency.

Mutational analysis of predicted active site residues of an exoglucanase secreted by Xanthomonas oryzae pv. oryzae to determine their role in catalysis and in virulence on rice.

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight disease in rice. As a part of its virulence repertoire, Xoo secretes a cell wall degrading enzyme Cellobiosidase (CbsA), which is a critical virulence factor and also a determinant of tissue specificity. CbsA protein is made up of an N-terminal catalytic domain and a C-terminal fibronectin type III domain. According to the CAZy classification, the catalytic domain of CbsA protein belongs to the glycosyl hydrolase-6 (GH6) family that performs acid-base catalysis. However, the identity of the catalytic acid and the catalytic base of CbsA is not known. Based on the available structural and biochemical data, we identified putative catalytic residues and probed them by site-directed mutagenesis. Intriguingly, the biochemical analysis showed that none of the mutations abolishes the catalytic activity of CbsA, an observation that is contrary to other GH6 family members. All the mutants exhibited altered enzymatic activity and caused significant virulence deficiency in Xoo emphasising the requirement of specific exoglucanase activity of wild-type CbsA for virulence on rice. Our study highlights the need for further studies and the detailed characterisation of bacterial exoglucanases.

Intracellular Toll-Like Receptors Modulate Adaptive Immune Responses in Head and Neck Cancer.

The percentage of head and neck cancer (HNC) positive for human papillomavirus (HPV) is unknown in most parts of India. How toll-like receptors (TLRs) affect the adaptive immune response in HNC is also mainly unknown. We here assessed the expressions of HPV DNA, p16, inflammation, and TLRs in oral squamous cell carcinoma (OC) and oropharyngeal squamous cell carcinoma (OPC). Patients with OC (n = 31) and OPC (n = 41), diagnosed during 2017-2018 at the Malabar Cancer Centre (tertiary cancer center), Kerala, India, were included in the study. Immunohistochemistry was performed on tumor specimens against p16, TLR3, TLR7, TLR8, TLR9, CD4, and CD8. Quantitate polymerase chain reaction for 14 high-risk HPVs (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68) was performed. Seven out of 31 OC (22.6%) were p16+ but only 3.2% (1/31) of OC were positive for HPV DNA. While 24.4% (10/41) of OPC were p16+, HPV DNA was found in only one P16+ OPC and in no P16- OPC. TLR3, TLR7, TLR8, and TLR9 were expressed both in OC and in OPC. The expression of TLR7 was significantly higher in OPC compared with OC. TLR8 expression was correlated with and TLR7 tended to be correlated with the inflammatory score in OPC (r = 0.56, p < 0.05 and r = 0.52, p = 0.08, respectively). In conclusion, the role of HPV in OC and OPC is minor, and p16 constitutes a poor biomarker for HPV positivity in Kerala, India. Intracellular TLRs are correlated with the degree of inflammation in OPC but not in OC and may potentially constitute a medical target in the therapy of HNC in the future.

The Impact of Diabetes on Morbidity and Mortality Following Thyroidectomy.

OBJECTIVES: To explore the association between diabetes and outcomes in thyroidectomy patients. METHODS: This retrospective cohort analysis used the 2015-2017 American College of Surgeons National Surgery Quality Improvement Program database. Current Procedural Terminology (CPT) codes were used to identify thyroidectomy cases (60210, 60212, 60220, 60225, 60240, 60252, 60254, 60260, 60270, and 60271). Demographics, comorbidities, and complication incidences were compared between diabetic and nondiabetic patients using Pearson's chi-square test/Fisher's exact test as appropriate. The independent effect of diabetes on outcomes was analyzed using binary logistic regression. RESULTS: A total of 47,776 (95.4%) nondiabetic and 2307 (4.6%) diabetic patients undergoing thyroidectomy were identified from 2015 to 2017. Chi-square analysis demonstrated that diabetic patients had higher incidences of obesity (55.2% vs. 33.2%; p < 0.001), dyspnea (12.7% vs. 4.8%; p < 0.001), poor functional status (1.9% vs. 0.4%; p < 0.001), ventilator dependence (0.6% vs. 0.1%; p < 0.001), chronic obstructive pulmonary disease (COPD; 6.8% vs. 2.2%; p < 0.001), congestive heart failure (1.1% vs. 0.3%; p < 0.001), acute renal failure (0.3% vs. 0.0%; p < 0.001), hypertension (79.2% vs. 32.4%; p < 0.001), dialysis (2.0% vs. 0.4%; p < 0.001), open wound (1.1% vs. 0.1%; p < 0.001), steroid use (5.3% vs. 2.3%; p < 0.001), bleeding disorders (3.6% vs. 0.9%; p < 0.001), preoperative blood transfusions (0.2% vs. 0.0%; p = 0.001), and systemic sepsis (1.0% vs. 0.3%; p < 0.001). Demographic characteristics were significantly different between the cohorts including gender (p < 0.001), age (p < 0.001), race (p < 0.001), and Hispanic ethnicity (p = 0.033). After adjusting for these factors, logistic regression analyses showed that diabetes was associated with acute renal failure (OR: 5.836; 95% CI: 1.060-32.134; p = 0.043), wound disruption (OR: 6.194; 95% CI: 1.752-21.900; p = 0.005), prolonged length of stay (OR: 1.430; 95% CI: 1.261-1.622; p < 0.001), unplanned readmission (OR: 1.380; 95% CI: 1.096-1.737; p = 0.006), superficial incisional surgical site infections (OR: 0.240; 95% CI: 0.058-0.995; p = 0.049), urinary tract infection occurrences (OR: 2.173; 95% CI: 1.186-3.980; p = 0.012), organ space surgical site infection occurrences (OR: 3.322; 95% CI: 1.016-10.864; p = 0.047), pneumonia occurrences (OR: 2.091; 95% CI: 1.125-3.884; p = 0.020), any medical complication (OR: 1.697; 95% CI: 1.246-2.313; p = 0.001), and any complication (OR: 1.495; 95% CI: 1.136-1.968; p = 0.004). CONCLUSION: Diabetes mellitus is a significant factor associated with increased odds of complications following thyroidectomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3628-3632, 2023.

Effect of Hypoalbuminemia in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism.

OBJECTIVES: Treatment for primary hyperparathyroidism is parathyroidectomy. This study identifies the association between hypoalbuminemia (HA) and outcomes in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: This retrospective cohort analysis utilized the 2006-2015 National Surgical Quality Improvement Program database. Current Procedure Terminology codes were used to identify patients undergoing parathyroidectomy for primary hyperparathyroidism. Prolonged length of stay (LOS) was defined as a duration of 2 days or greater. Demographics and comorbidities were compared between HA (serum albumin <3.5 g/dL) and non-HA cohorts using chi-square analysis. The independent effect of HA on adverse outcomes was analyzed using binary logistic regression. RESULTS: A total of 7183 cases with primary hyperparathyroidism were classified into HA (n = 381) and non-HA (n = 6802) cohorts. HA patients had increased complications, including renal insufficiency (0.8% vs. 0.0%, p = 0.001), sepsis (1.0% vs. 0.1%, p = 0.003), pneumonia (0.8% vs. 0.1%, p = 0.018), acute renal failure (1.0% vs. 0.0%, p < 0.001), and unplanned intubation (1.3% vs. 0.2%, p = 0.004). HA patients had increased risk of death (1.6% vs. 0.1%, p < 0.001), prolonged LOS (40.9% vs. 6.3%, p < 0.001), and any complication (5.5% vs. 1.2%, p < 0.001). Adjusted binary logistic regression indicated HA patients experienced increased odds of progressive renal insufficiency (OR 18.396, 95% CI 1.844-183.571, p = 0.013), prolonged LOS (OR 4.892; 95% CI 3.571-6.703; p < 0.001), unplanned reoperation (OR 2.472; 95% CI 1.012-6.035; p = 0.047), and unplanned readmission (OR 3.541; 95% CI 1.858-6.748; p < 0.001). CONCLUSIONS: HA may be associated with adverse complications in patients undergoing parathyroidectomy for primary hyperparathyroidism. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2035-2039, 2023.

Frequency of EGFR mutations in lung adenocarcinoma patients - A study from tertiary cancer center of South India.

BACKGROUND AND OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation analysis has become an important part of the initial workup of non-squamous non-small cell lung cancer (NS-NSCLC) patients. This study is attempted as South Indians population is comprised of ethnic groups with diverse genetic makeup and only very limited data on EGFR mutation is available from south India. A detailed understanding of EGFR mutation profile will help in better planning of treatment strategies and resource allocation. METHODS: A retrospective analysis of EGFR mutation frequency in 350 patients diagnosed with adenocarcinoma of lung and its association with pathological characteristics was done. RESULTS: Out of 350 cases of pulmonary adenocarcinoma, within an age group ranging from 30 to 86 years. EGFR mutations were identified in 34.8% (n = 122) cases, out of which 35.24% (n = 43) were in non-smoker females (P = 0.001). Of the 14 cases with resistant type of EGFR mutations, nine were in smoker males and the remaining five in non-smoker females. INTERPRETATION AND CONCLUSION: Overall EGFR mutation frequency observed in our study was similar to other Indian studies. However, in our study, we observed that mutation in exon 21 was less frequent compared to other studies. A similar slightly increased frequency of rare mutations and double mutations were observed in our study. A detailed study of the molecular epidemiology of lung cancer and its association with different geographical zones of India is needed. This understanding will help in better planning of treatment strategies and resource allocation.

Role of the FnIII domain associated with a cell wall-degrading enzyme cellobiosidase of Xanthomonas oryzae pv. oryzae.

Cellobiosidase (CbsA) is an important secreted virulence factor of Xanthomonas oryzae pv. oryzae (Xoo), which causes bacterial blight of rice. CbsA is one of several cell wall-degrading enzymes secreted by Xoo via the type II secretion system (T2SS). CbsA is considered a fundamental virulence factor for vascular pathogenesis. CbsA has an N-terminal glycosyl hydrolase domain and a C-terminal fibronectin type III (FnIII) domain. Interestingly, the secreted form of CbsA lacks the FnIII domain during in planta growth. Here we show that the presence of the FnIII domain inhibits the enzyme activity of CbsA on polysaccharide substrates like carboxymethylcellulose. The FnIII domain is required for the interaction of CbsA with SecB chaperone, and this interaction is crucial for the stability and efficient transport of CbsA across the inner membrane. Deletion of the FnIII domain reduced virulence similar to ΔcbsA Xoo, which corroborates the importance of the FnIII domain in CbsA. Our work elucidates a hitherto unknown function of the FnIII domain in enabling the virulence-promoting activity of CbsA.

MiRNA expression profiling and emergence of new prognostic signature for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analysis revealed the signature miRNAs to be involved in various cancer associated pathways. Up-regulation of miR-196a, miR-21, miR-1237 and downregulation of miR-204, miR-144 was associated with poor prognosis of OSCC patients. The mir-196a/miR-204 expression ratio emerged as best predictor for disease recurrence and patient survival. Altogether, our study identified a miRNA signature for OSCC with prognostic significance.

Clinical outcomes of pediatric patients with autism spectrum disorder and other neurodevelopmental disorders and intracranial germ cell tumors.

INTRODUCTION: Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Given the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs) in patients with IGCTs and characterized outcomes for patients with NDD and IGCTs. METHODS: A retrospective review of medical records was conducted for 111 patients diagnosed with IGCTs between 1998 and 2018 and evaluated at the Massachusetts General Hospital. Kaplan-Meier method and log-rank test was used for survival analyses. Cox regression analyses were performed for parameters associated with progression-free survival (PFS). RESULTS: Median age at IGCT diagnosis was 12.8 years (range: 4.3-21.7) and median follow-up was 6.5 years (range: 0.2-20.5). Eighteen patients were diagnosed with NDDs prior to IGCT diagnosis, including five patients with autism spectrum disorder (ASD). Of the 67 patients with pure germinomas, four (6.0 %) had prior ASD diagnoses. Patients with NDD had significantly inferior PFS in the nongerminomatous germ cell tumor (NGGCT) cohort. On univariate and multivariable analyses, craniospinal irradiation (CSI) was significantly associated with improved PFS in the NGGCT cohort. CONCLUSIONS: Our study found an ASD prevalence in the pure germinoma cohort more than threefold greater than the national prevalence, suggesting an association between ASD and pure germinomas. Furthermore, patients with NDD and NGGCT had worse PFS, possibly due to fewer patients with NDD receiving CSI. Future prospective studies with larger cohorts are needed to examine associations between NDDs and IGCTs, and further characterize outcomes for patients with NDDs and IGCTs.

Preferential Use of Stainless Steel Crowns as a Strategy to Minimize Retreatment of Primary Molars under General Anesthesia.

Purpose: The purpose of this study was to investigate whether primary molars treated with composite resins (CRs) and stainless steel crowns (SSCs) during an oral rehabilitation under general anesthesia (GA1) required retreatment at a second oral rehabilitation under GA (GA2). Methods: Records were examined from 296 healthy patients with more than one dental rehabilitation under general anesthesia from June 2012 to January 2019. Data included treatment details and demographic information. Frequencies and means were recorded. An analysis was completed using logistic regression and chi-square for categorical variables. Results: For primary first molars, 43 percent of CRs placed at GA1 were treated with SSCs at GA2. For primary second molars, 35 percent of CRs placed at GA1 were treated with SSCs at GA2. There was no statistically significant difference in retreatment rates by molar type (P equals 0.27). Eight percent of SSCs placed on any molar at GA1 required retreatment at GA2. Conclusions: Primary molars treated with stainless steel crowns using general anesthesia had the lowest percentage of retreatment compared to those treated with composite resins. Strong consideration should be given to the placement of SSCs on primary molars in patients with early childhood caries under general anesthesia. Placement of primary molar SSCs during initial treatment under general anesthesia may reduce the need for additional treatment in the future.

Loss of CDKN2A and CDKN2B expression is associated with disease recurrence in oral cancer.

BACKGROUND: Loco-regional recurrence is one of the major reasons for poor prognosis of oral squamous cell carcinoma (OSCC). However, till date, no feasible molecular marker is available to predict the risk of recurrence in OSCC patients. AIM: To evaluate the cell cycle regulatory genes expression and its association with the risk of recurrence in oral cancer patients. MATERIALS AND METHODS: Transcript level expressions of 47 cell cycle regulatory genes were analyzed in 73 OSCC tumors from buccal mucosa and tongue, 26 adjacent normal samples using real-time polymerase chain reaction. TaqMan low-density array data were analyzed using the DataAssist™ v 3.01. Significantly altered genes within the tumor samples and samples showing recurrence (re-appearance of disease during the follow-up in cases having complete response to initial treatment assessed after 3 months of the treatment) were identified. Further, Kyoto Encyclopedia of Genes and Genomes pathway analysis and The Cancer Genome Atlas (TCGA) online data analysis portal were used to analyze interacting protein and pathways significantly associated with the altered gene. RESULTS: CCNA1, CCNB2, CCND2, CCNE1, CCNF, CDC2, CDK6, CHEK1, and TGFA found to significantly alter in the tumor sample of oral cancer patients, and down-expression of CDKN2A and CDKN2B found to associate with the recurrence of disease in oral cancer patients. TCGA data also showed the loss of CDKN2A and CDKN2B significantly associated with recurrence in head and neck cancer patients. CONCLUSION: CDKN2A and CDKN2B expression analysis can be used as the prognostic marker for the oral cancer patients. The present method of data analysis helps overcome the limitations and complications of high throughput techniques and thereby increases the opportunity of employing molecular markers in routine clinical management of OSCC.

Effects of Processing on a Sustained Release Formulation Prepared by Twin-Screw Dry Granulation.

Dry granulation is an indispensable process used to improve the flow property of moisture-sensitive materials. Considering the limitations of currently available dry granulation techniques, it is necessary to develop a novel technique. In this study, a twin-screw dry granulation (TSDG) technology was successfully applied to produce a sustained-release dry granule formulation, which was subsequently compressed into sustained-release tablets. Based on a preliminary study, theophylline was selected as model drug, Klucel™ EF, Ethocel™, and magnesium stearate were selected as excipients. A Resolution V Irregular Fraction Design was applied to determine the effect of different processing parameters (screw speed, feeding rate, barrel temperature, and screw configuration) on product properties (flow properties, particle size distribution, and dissolution time). A reliable model was achieved by combining the data obtained, and processing parameters were automatically optimized to attain the setting goal. In general, TSDG was demonstrated to be an alternative method for the preparation of dry granules. The continuous processing nature, simplicity of operation, and ease of optimization made TSDG competitive compared with other conventional dry granulation techniques.

Evolutionary Features in the Structure and Function of Bacterial Toxins.

Toxins can function both as a harmful and therapeutic molecule, depending on their concentrations. The diversity in their function allows us to ask some very pertinent questions related to their origin and roles: (a) What makes them such effective molecules? (b) Are there evolutionary features encoded within the structures of the toxins for their function? (c) Is structural hierarchy in the toxins important for maintaining their structure and function? (d) Do protein dynamics play a role in the function of toxins? and (e) Do the evolutionary connections to these unique features and functions provide the fundamental points in driving evolution? In light of the growing evidence in structural biology, it would be appropriate to suggest that protein dynamics and flexibility play a much bigger role in the function of the toxin than the structure itself. Discovery of IDPs (intrinsically disorder proteins), multifunctionality, and the concept of native aggregation are shaking the paradigm of the requirement of a fixed three-dimensional structure for the protein's function. Growing evidence supporting the above concepts allow us to redesign the structure-function aspects of the protein molecules. An evolutionary model is necessary and needs to be developed to study these important aspects. The criteria for a well-defined model would be: (a) diversity in structure and function, (b) unique functionality, and (c) must belong to a family to define the evolutionary relationships. All these characteristics are largely fulfilled by bacterial toxins. Bacterial toxins are diverse and widely distributed in all three forms of life (Bacteria, Archaea and Eukaryotes). Some of the unique characteristics include structural folding, sequence and functional combination of domains, targeting a cellular process to execute their function, and most importantly their flexibility and dynamics. In this work, we summarize certain unique aspects of bacterial toxins, including role of structure in defining toxin function, uniqueness in their enzymatic function, and interaction with their substrates and other proteins. Finally, we have discussed the evolutionary aspects of toxins in detail, which will help us rethink the current evolutionary theories. A careful study, and appropriate interpretations, will provide answers to several questions related to the structure-function relationship of proteins, in general. Additionally, this will also allow us to refine the current evolution theories.

Sensory Gating Deficits and their Clinical Correlates in Drug-Free/Drug-Naive Patients with Schizophrenia.

BACKGROUND: Sensory gating refers to "filtering" of irrelevant sensory input in the brain. Auditory sensory gating deficit has been considered as a marker of schizophrenia (SCZ) and assessed using P50 paired-click paradigm. We explore sensory gating deficits and their clinical correlates in SCZ. MATERIALS AND METHODS: Twenty-five drug-free/drug-naïve patients with SCZ, whose psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS), and 25 age-matched normal controls (NC) were recruited. ERP recordings were done using 40-channel event-related potential measuring system. RESULTS: S2-S1 P50 amplitude difference, an index of sensory gating, was significantly lower in SCZ at F3 and F4 sites when compared to NC, indicating impaired gating. SCZ had significantly lower S1 amplitude compared to NC at these sites; S2 amplitudes were comparable. The sensory gating index also showed significant correlations with PANSS scores. CONCLUSIONS: Our study reiterates sensory gating abnormalities in SCZ and confers a frontal specificity, implying specific deficits in early preattentive processes to them. Further, we suggest that gating deficits in SCZ are driven predominantly by abnormally small S1 rather than an inability to suppress S2. A correlation between sensory gating parameters and measures of psychopathology strengthens the hypothesis that abnormal response to sensory input may contribute to the psychopathology in SCZ.

Cyclin D1 overexpression associated with activation of STAT3 in oral carcinoma patients from South India.

BACKGROUND: Our previous study showed that overexpression of cyclin D1 protein is associated with poor prognosis in oral squamous cell carcinoma (OSCC) patients. Regarding the alteration in the transactivating pathway regulating cyclin D1 expression is still unclear in OSCC from our population. OBJECTIVES: The major objective of this study is to understand the alteration associated with the transactivation pathway regulating the cyclin D1 overexpression in OSCC patients from our population. MATERIALS AND METHODS: Alteration in the transactivation pathway regulating cyclin D1 expression was evaluated in tumor sample from OSCC patients. The findings were further validated using in vitro knockdown model in OSCC cell line. RESULTS: Results from the patients' samples showed that the Phospho-STAT3 has a significant association with cyclin D1 overexpression in OSCC tumor samples. Further knockdown in vitro studies using SCC66 showed a significant correlation between STAT3 and cyclin D1 in OSCC. CONCLUSION: The results from this study showed that in our population the cyclin D1 overexpression is associated with hyperactivation of STAT3 pathway. Our previous result has shown that the cyclin D1 protein overexpression is associated with poor prognosis in OSCC patients. Hence, STAT3 pathway will be better target for the patients with increased cyclin D1 in OSCC patients from our population.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

BACKGROUND: Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS: The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS: Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend <.0001), with a joinpoint for increased use noted in 2006 (P<.0001). Higher SBRT use was found to be associated with longer travel distance for treatment, younger age, white race, more affluent zip code of residence, academic treatment center, favorable disease characteristics, and fewer comorbidities (all P<.0001). Compared with travel distances <25 miles for treatment, travel distances of 25 to 50 miles and >50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P < .0001). CONCLUSIONS: Definitive prostate SBRT use increased more than 3-fold since 2004, with a significant increase in use coinciding with early reports of short-term efficacy. Long-distance travel for treatment was associated with greater than twice the odds of receipt of definitive prostate SBRT compared with short-distance travel, suggesting that treatment decisions with unknown long-term clinical implications may be strongly driven by sociodemographic factors. Cancer 2018;124:1141-9. © 2017 American Cancer Society.

A mutation in an exoglucanase of Xanthomonas oryzae pv. oryzae, which confers an endo mode of activity, affects bacterial virulence, but not the induction of immune responses, in rice.

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight, a serious disease of rice. Xoo secretes a repertoire of cell wall-degrading enzymes, including cellulases, xylanases and pectinases, to degrade various polysaccharide components of the rice cell wall. A secreted Xoo cellulase, CbsA, is not only a key virulence factor of Xoo, but is also a potent inducer of innate immune responses of rice. In this study, we solved the crystal structure of the catalytic domain of the CbsA protein to a resolution of 1.86 Å. The core structure of CbsA shows a central distorted TIM barrel made up of eight ß strands with N- and C-terminal loops enclosing the active site, which is a characteristic structural feature of an exoglucanase. The aspartic acid at the 131st position of CbsA was predicted to be important for catalysis and was therefore mutated to alanine to study its role in the catalysis and biological functions of CbsA. Intriguingly, the D131A CbsA mutant protein displayed the enzymatic activity of a typical endoglucanase. D131A CbsA was as proficient as wild-type (Wt) CbsA in inducing rice immune responses, but was deficient in virulence-promoting activity. This indicates that the specific exoglucanase activity of the Wt CbsA protein is required for this protein to promote the growth of Xoo in rice.

Analysis of patient outcomes following proton radiation therapy for retinoblastoma.

PURPOSE: Proton radiotherapy (PRT) is used in the treatment of retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to radiation and thus decrease risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. METHODS: RB patients treated with PRT at our institution between 1986 and 2012 were invited to return for participation in a study designed to assess long-term outcomes. Enrolled patients underwent comprehensive analysis including oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. RESULTS: A total of 12 patients were enrolled in this study, and the average length of follow-up among enrolled patients was 12.9 years (range 4.8-22.2 years). All enrolled patients had bilateral disease, and the disease and visual outcomes for enrolled patients were similar to outcomes for all RB patients treated with PRT over the same time period at our institution. Endocrine evaluation revealed no growth abnormalities or hormonal deficiencies across the cohort. Based on MRI and external cephalometry, PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that RB treatment did not appear to severely impact long-term QOL. CONCLUSIONS: In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort.

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques.

This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug.