Dynamic Microparticle Assembly at the Interface of Chemoresponsive Liquid Crystal Droplets.

The confinement of liquid crystals (LCs) in spherical microdroplets results in exotic internal configurations and topological defects in response to physical and chemical stimuli. Recent exploration into the placement of colloids on the surface of LC microdroplets has led to the design of a new class of functional materials with patterned surface properties. It is established that the placement of a colloid on a LC droplet surface can pin the topological defect at the interface, thereby restricting changes in the LC configuration. Herein, we build upon the handful of reports published to provide a fundamental understanding of the colloid positioning in response to external stimuli. Using polystyrene (PS) colloids, we explored the dynamics of particle self-assembly in response to an interfacial enzymatic breakdown of poly-l-lysine by trypsin. We found that for a significant population of droplets, the positioning of the colloid is unaffected by the changes in the internal ordering of LC. Inspired by the new observations, we delved deeper to understand the role of interfacial stabilizers in modulating the preferential alignment of LC and the placement of colloidal microparticles. We also demonstrated that for a certain population of droplets, the positioning of the colloids remains unperturbed in response to multistep reversible adsorption of interfacial amphiphiles. Our findings reveal interesting possibilities of correlating the stimuli-responsive switching of internal configurations of LC with colloid placement on the particle-decorated LC droplets.

Machine learning can guide suitability of consultation and patient referral through telemedicine for hepatobiliary diseases.

BACKGROUND AND AIM: Telemedicine is an evolving tool to provide health-care services. We evaluated the suitability of telemedicine to deliver effective consultation for hepatobiliary disorders. METHODS: In this prospective study spanning over a year, we interviewed hepatologists delivering the teleconsultations through a pre-validated questionnaire. A consult was deemed suitable based on the physician's judgment in the absence of unplanned hospitalization. We evaluated factors determining the suitability through inferential statistics and machine learning models, namely, extreme gradient boosting (XGB) and decision tree (DT). RESULTS: Of 1118 consultations, 917 (82.0%) were deemed suitable. On univariable analysis, patients with skilled occupation, higher education, out-of-pocket expenses, and diseases such as chronic hepatitis B, C, and non-alcoholic fatty liver disease (NAFLD) without cirrhosis were associated with suitability (P < 0.05). Patients with cirrhosis (compensated or decompensated), acute-on-chronic liver failure (ACLF), and biliary obstruction were likely unsuitable (P < 0.05). XGB and DT models predicted suitability with an area under the receiver operating curve of 0.808 and 0.780, respectively. DT demonstrated that compensated cirrhosis with higher education or skilled occupation with age < 55 years had 78% chance of suitability whereas hepatocellular carcinoma, decompensated cirrhosis, and ACLF patients were unsuitable with a 60-95% probability. In non-cirrhotic liver diseases, hepatitis B, C, and NAFLD were suitable, with a probability of 89.7%. Biliary obstruction and previous failure of teleconsultation were unsuitable, with a probability of 70%. Non-cirrhotic portal fibrosis, dyspepsia, and dysphagia not requiring intervention were suitable (probability: 88%). CONCLUSION: A simple decision tree can guide the referral of unsuitable and the management of suitable patients with hepatobiliary diseases through telemedicine.

Probing photodissociation dynamics using ring polymer molecular dynamics.

The performance of the ring polymer molecular dynamics (RPMD) approach to simulate typical photodissociation processes is assessed. The correct description of photodissociation requires the calculation of correlation functions or expectation values associated with non-equilibrium initial conditions, which was shown to be possible with RPMD very recently [J. Chem. Phys. 145, 204118 (2016)]. This approach is combined with treatment of the nonadiabatic dynamics employing the ring polymer surface hopping approach (RPSH), which is based on Tully's fewest switches surface hopping (FSSH) approach. The performance is tested using one-dimensional photodissociation models. It is found that RPSH with non-equilibrium initial conditions can well reproduce the time-dependent dissociation probability, and adiabatic and diabatic populations for cases where the crossing point is below and above the Franck-Condon point, respectively, while standard FSSH fails to reproduce the exact quantum dynamics in the latter case. Thus, it is shown that RPSH is an efficient and accurate alternative to standard FSSH, which is one of the most widely employed approaches to study photochemistry.

Isostructural unbranched alkyl-chains as tools for stabilizing ß-turn structure.

To investigate the structural role played by isostructural unbranched alkyl-chains on the conformational ensemble and stability of ß-turn structures, the conformational properties of a designed model peptide: Plm-Pro-Gly-Pda (1, Plm: H3 C-(CH2)14-CONH-; Pda: -CONH- (CH2 )14 -CH3) have been examined and compared with the parent peptide: Boc-Pro-Gly-NHMe (2, Boc: tert-butoxycarbonyl; NHMe: N-methylamide). The characteristic (13)C NMR chemical-shifts of the Pro C(ß) and C(γ) resonances ascertained the incidence of an all-trans peptide-bond in low polarity deuterochloroform solution. Using FTIR and (1) H NMR spectroscopy, we establish that apolar alkyl-chains flanking a ß-turn promoting Pro-Gly sequence impart definite incremental stability to the well-defined hydrogen-bonded structure. The assessment of (1)H NMR derived thermodynamic parameters of the hydrogen-bonded amide-NHs via variable temperature indicate that much weaker hydrophobic interactions do contribute to the stability of folded reverse turn structures. The far-UV CD spectral patterns of 1 and 2 in 2,2,2-trifluoroethanol are consistent with Pro-Gly specific type II ß-turn structure, concomitantly substantiate that the flanking alkyl-chains induce substantial bias in enhanced ß-turn populations. In view of structural as well as functional importance of the Pro-Gly mediated secondary structures, besides biochemical and biological significance of proteins lipidation via myristoylation or palmytoilation, we highlight potential convenience of the unbranched Plm and Pda moieities not only as main-chain N- and C-terminal protecting groups but also to mimic and stabilize specific isolated secondary and supersecondary structural components frequently observed in proteins and polypeptides.

Rising Incidence of Post Covid Rhinocerebral Mucormycosis: An Otolaryngologists Prospective.

Mucormycosis or grimmer popular name, "black fungus" has evolved public concern in context of covid-19 pandemic, Covid Associated Mucormycosis (CAM) seen in Covid-19 pandemic and as a post covid sequelae. The present study was conducted to find out the incidence of the Mucormycosis, and to study its association with post-covid status and co-morbidities. A retrospective study conducted at tertiary care centre over a period of four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease. 59 patients had CAM, 47 patients had rhino-orbital Mucormycosis, followed by nasal and paranasal Mucormycosis in 8 patients, 3 patients with rhino-orbital-cerebral Mucormycosis, and one patient with pulmonary Mucormycosis. Diabetes mellitus was present in all 59 patients, 60.41% who had HbA1c > 10 (range 7-15), and 39.58% had HbA1c < 10 with range 6-13. Only 8.33% had controlled diabetes status, uncontroled hypertension and diabetes was seen in 34.02%. All patients were started with IV amphotericin B anti-fungal drug, and followed by oral posaconazole. Depending upon the extent of the disease surgical debridement was done in 52 patients. All patients had history of steroid intake. 7 mortality was there. Uncontrolled diabetes, over-zealous use of steroids, uncontrolled underlying primary disease or co-morbidities, prolonged hospitalization in intensive care unit or normal wards, and hyperventilation all these factors together aggravated the CAM. So it's proper management based on, prompt diagnosis, reversal of predisposing condition with proper medical and aggressive surgical debridement remain the corner stone for this deadly CAM.

An Experience of Otorhinolaryngologists as Frontline Worker with Novel Coronavirus: A Qualitative Analysis.

During this COVID pandemic healthcare worker systems were overwhelmed. Doctors especially otorhinolaryngologists in addition to doing their specialty duty were also recruited to provide care to COVID-19 patients. To our knowledge, no studies about their experiences regarding COVID-19 have been published. Present study aimed to describe the experiences of Otorhinolaryngologist during this pandemic. This is a qualitative study using an empirical phenomenological approach. 30 ENT doctors were recruited from government and private sector. They participated in semi-structured, in-depth interviews by telephone in a period of one month. Interviews were recorded by consent and data was analyzed. After analysis four themes were revealed namely; 'nature of duty during Covid-19 pandemic', 'modification made to adjust the duty', 'conflict between professional duty and family responsibilities', and 'fear of pandemic ill effect on their health'. The extreme work and fatigue drained ours ENT doctor's physically as well as emotionally. But our doctors showed their resilience and the spirit of professional dedication to overcome difficulties. Comprehensive support should be provided to safeguard the wellbeing of health-care providers mainly doctors. In the meantime timely as well as intensive training for all healthcare worker is highly recommended to promote preparedness and improve efficacy during the pandemic.

Feasibility, Outcomes, and Safety of Telehepatology Services During the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has hampered health care delivery globally. We evaluated the feasibility, outcomes, and safety of telehepatology in delivering quality care amid the pandemic. A telemedicine setup using smartphones by hepatologists was organized at our tertiary-care center after pilot testing. Consecutive patients availing telehepatology services were recruited between March and July 2020. An adapted model for assessment of telemedicine was used after validity and reliability testing, to evaluate services 7-21 days after index teleconsultation. Of the 1,419 registrations, 1,281 (90.3%) consultations were completed. From 245 randomly surveyed patients, 210 (85.7%) responded (age [years, interquartile range]: 46 [35-56]; 32.3% females). Seventy percent of patients belonged to the middle or lower socio-economic class, whereas 61% were from rural areas. Modes of teleconsultation were audio (54.3%) or hybrid video call (45.7%). Teleconsultation alone was deemed suitable in 88.6% of patients. Diagnosis and compliance rates were 94% and 82.4%, respectively. Patients' convenience rate, satisfaction rate, improvement rate, success rate, and net promoter scores were 99.0%, 85.2%, 49.5%, 46.2% and 70, respectively. Physical and mental quality of life improved in 67.1% and 82.8% of patients, respectively, following index teleconsultation. Person-hours and money spent by patients were significantly lower with teleconsultation (P < 0.001); however, person-hours spent by hospital per teleconsultation were higher than in physical outpatient services (P < 0.001). Dissatisfied patients were more likely to have lower diagnosis rate, unsuitability for teleconsultation, noncompliance, poorer understanding, and uncomfortable conversation during teleconsultation. Connectivity issues (22.9%) were the most common barrier. Three patients, all of whom were advised emergency care during teleconsultation, succumbed to their illness. Conclusion: Telehepatology is a feasible and reasonably effective tool for rendering health care services using smartphones during the COVID-19 pandemic. Systematic implementation, possible integration into routine health care delivery, and formal cost-effectiveness of telehepatology services need further exploration.

Volatile chemicals from leaf litter are associated with invasiveness of a neotropical weed in Asia.

Some invasive plant species appear to strongly suppress neighbors in their nonnative ranges but much less so in their native range. We found that in the field in its native range in Mexico, the presence of Ageratina adenophora, an aggressive Neotropical invader, was correlated with higher plant species richness than found in surrounding plant communities where this species was absent, suggesting facilitation. However, in two nonnative ranges, China and India, A. adenophora canopies were correlated with much lower species richness than the surrounding communities, suggesting inhibition. Volatile organic compound (VOC) signals may contribute to this striking biogeographical difference and the invasive success of A. adenophora. In controlled experiments volatiles from A. adenophora litter caused higher mortality of species native to India and China, but not of species native to Mexico. The effects of A. adenophora VOCs on seedling germination and growth did not differ between species from the native range and species from the nonnative ranges of the invader. Litter from A. adenophora plants from nonnative populations also produced VOCs that differed quantitatively in the concentrations of some chemicals than litter from native populations, but there were no chemicals unique to one region. Biogeographic differences in the concentrations of some volatile compounds between ranges suggest that A. adenophora may be experiencing selection on biochemical composition in its nonnative ranges.

Factors associated with preservation of facial nerve function after surgical resection of vestibular schwannoma.

Avoidance of facial nerve palsy is one of the major goals of vestibular schwannoma (VS) microsurgery. In this study, we examined the significance of previously implicated prognostic factors (age, tumor size, the extent of resection and the surgical approach) on post-operative facial nerve function. We selected all VS patients from prospectively collected database (1984-2009) who underwent microsurgical resection as their initial treatment for histopathologically confirmed VS. The effect of variables such as surgical approach, tumor size, patient age and extent of resection on rates facial nerve dysfunction after surgery, were analyzed using multivariate logistic regression. Patients with preoperative facial nerve dysfunction (House-Brackman [HB] score 3 or higher) were excluded, and HB grade of 1 or 2 at the last follow-up visit was defined as "facial nerve preservation." A total of 624 VS patients were included in this study. Multivariate logistic regression analysis found that only pre-operative tumor size significantly predicted poorer facial nerve outcome for patients followed-up for ≥6 and ≥12 months (OR 1.27, 95% CI 1.09-1.49, p < 0.01; OR 1.35, 95% CI 1.10-1.67, P < 0.01, respectively). We found no significant relationship between facial nerve function and age, extent of resection, surgical approach, or tumor size (when extent of resection and surgical approach were included in the regression analysis). Because facial nerve palsy is a debilitating and psychologically devastating condition for the patient, we suggest altering surgical aggressiveness in patients with unfavorable tumor anatomy, particularly in cases with large tumors where overaggressive resection might subject the patient to unwarranted risk. Residual disease can be followed and controlled with radiosurgery if interval growth is noted.

Craniopharyngioma: a comparison of tumor control with various treatment strategies.

OBJECT: Craniopharyngiomas have a propensity to recur after resection, potentially causing death through their aggressive local behavior in their critical site of origin. Recent data suggest that subtotal resection (STR) followed by adjuvant radiotherapy (XRT) may be an appealing substitute for gross-total resection (GTR), providing similar rates of tumor control without the morbidity associated with aggressive resection. Here, the authors summarize the published literature regarding rates of tumor control with various treatment modalities for craniopharyngiomas. METHODS: The authors performed a comprehensive search of the English language literature to identify studies publishing outcome data on patients undergoing surgery for craniopharyngioma. Rates of progression-free survival (PFS) and overall survival (OS) were determined through Kaplan-Meier analysis. RESULTS: There were 442 patients who underwent tumor resection. Among these patients, GTR was achieved in 256 cases (58%), STR in 101 cases (23%), and STR+XRT in 85 cases (19%). The 2- and 5-year PFS rates for the GTR group versus the STR+XRT group were 88 versus 91%, and 67 versus 69%, respectively. The 5- and 10-year OS rates for the GTR group versus the STR+XRT group were 98 versus 99%, and 98 versus 95%, respectively. There was no significant difference in PFS (log-rank test) or OS with GTR (log-rank test). CONCLUSIONS: Given the relative rarity of craniopharyngioma, this study provides estimates of outcome for a variety of treatment combinations, as not all treatments are an option for all patients with these tumors.

Glioblastoma-Derived IL6 Induces Immunosuppressive Peripheral Myeloid Cell PD-L1 and Promotes Tumor Growth.

PURPOSE: Upregulation of programmed death-ligand 1 (PD-L1) on circulating and tumor-infiltrating myeloid cells is a critical component of GBM-mediated immunosuppression that has been associated with diminished response to vaccine immunotherapy and poor survival. Although GBM-derived soluble factors have been implicated in myeloid PD-L1 expression, the identity of such factors has remained unknown. This study aimed to identify factors responsible for myeloid PD-L1 upregulation as potential targets for immune modulation. EXPERIMENTAL DESIGN: Conditioned media from patient-derived GBM explant cell cultures was assessed for cytokine expression and utilized to stimulate naïve myeloid cells. Myeloid PD-L1 induction was quantified by flow cytometry. Candidate cytokines correlated with PD-L1 induction were evaluated in tumor sections and plasma for relationships with survival and myeloid PD-L1 expression. The role of identified cytokines on immunosuppression and survival was investigated in vivo utilizing immunocompetent C57BL/6 mice bearing syngeneic GL261 and CT-2A tumors. RESULTS: GBM-derived IL6 was identified as a cytokine that is necessary and sufficient for myeloid PD-L1 induction in GBM through a STAT3-dependent mechanism. Inhibition of IL6 signaling in orthotopic murine glioma models was associated with reduced myeloid PD-L1 expression, diminished tumor growth, and increased survival. The therapeutic benefit of anti-IL6 therapy proved to be CD8+ T-cell dependent, and the antitumor activity was additive with that provided by programmed death-1 (PD-1)-targeted immunotherapy. CONCLUSIONS: Our findings suggest that disruption of IL6 signaling in GBM reduces local and systemic myeloid-driven immunosuppression and enhances immune-mediated antitumor responses against GBM.

Fine needle aspiration cytology of IgG4-related disease: A potential diagnostic pitfall?

BACKGROUND: IgG4-related disease (IgG4-RD) is a tumefactive fibro-inflammatory lesion that can affect any organ system in the body. Till date, no cytological data on IgG4-RD are available and this is the first study depicting the cytopathology features of IgG4-RD. AIM AND OBJECTIVE: To describe the cytopathological features and potential diagnostic errors of IgG4-RD. MATERIALS AND METHODS: The cytological features of 10 histopathology proven IgG4-RD cases (11 samples) were retrospectively reviewed along with corresponding histopathology. RESULTS: The cellularity of the cytology smears was low (36.4%) to moderate (45.4%) to high (18.1%). The low cellularity correlated well with the pattern C in histopathology (predominant fibrosis pattern). The non-epithelial background showed a preponderance of lymphocytes along with polymorphs and spindle-shaped fibroblasts. Most of these cases showed the presence of plasma cells and eosinophils. Epithelial atypia was seen in 18.2% cases. CONCLUSION: The causes of misdiagnosis were low cellularity, epithelial atypia, and non-representative background. The important diagnostic clues to suspect a diagnosis of IgG4-RD include low cellularity despite adequate effort, inflammatory background rich in lymphocytes and spindle cells admixed with a few plasma cells and eosinophils along with radiological features and raised serum IgG4 Diagn. Cytopathol. 2017;45:14-21. © 2016 Wiley Periodicals, Inc.

Digital image classification with the help of artificial neural network by simple histogram.

BACKGROUND: Visual image classification is a great challenge to the cytopathologist in routine day-to-day work. Artificial neural network (ANN) may be helpful in this matter. AIMS AND OBJECTIVES: In this study, we have tried to classify digital images of malignant and benign cells in effusion cytology smear with the help of simple histogram data and ANN. MATERIALS AND METHODS: A total of 404 digital images consisting of 168 benign cells and 236 malignant cells were selected for this study. The simple histogram data was extracted from these digital images and an ANN was constructed with the help of Neurointelligence software [Alyuda Neurointelligence 2.2 (577), Cupertino, California, USA]. The network architecture was 6-3-1. The images were classified as training set (281), validation set (63), and test set (60). The on-line backpropagation training algorithm was used for this study. RESULT: A total of 10,000 iterations were done to train the ANN system with the speed of 609.81/s. After the adequate training of this ANN model, the system was able to identify all 34 malignant cell images and 24 out of 26 benign cells. CONCLUSION: The ANN model can be used for the identification of the individual malignant cells with the help of simple histogram data. This study will be helpful in the future to identify malignant cells in unknown situations.

A rare case report and appraisal of the literature on spontaneous tooth exfoliation associated with trigeminal herpes zoster.

BACKGROUND: Reports of post herpetic maxillofacial complications have been very rarely documented in the literature that includes periapical lesions, calcified and devitalized pulps, resorption of roots, osteonecrosis, and spontaneous exfoliation of teeth. The atypical feature of the case of concern to the dental surgeon is the rare complication of spontaneous tooth exfoliation following herpes zoster. CASE REPORT: This case reports a male patient of age 47 years who reported to the Department of Periodontology with the chief complaint of mobility in the left upper central incisor. Patient history revealed herpes zoster infection that began 11 days earlier along with underlying diabetes mellitus condition. We hereby report a known diabetic patient with history of herpes zoster infection who presented with rare complication of spontaneous tooth exfoliation involving the maxillary division of the trigeminal nerve. DISCUSSION: Limited number of cases has been reported in the literature regarding spontaneous teeth exfoliation secondary to herpes zoster. The exact pathogenesis regarding the spontaneous exfoliation of teeth in herpes zoster patient is still controversial. Thus, an oral health care provider should be aware of this rare complication while managing a case of tooth mobility with the previous history of herpes zoster of trigeminal nerve.

Safety and outcomes of preoperative embolization of intracranial hemangioblastomas: A systematic review.

INTRODUCTION: While preoperative embolization is often reserved for large and highly vascular tumors in order to minimize blood loss, its safety and efficacy in the treatment of hemangioblastomas (HB) is unclear. We present the largest systematic review focusing on the safety and outcome of preoperative embolization of intracranial HB. MATERIALS AND METHODS: To identify all cases of preoperative embolization for HB, a literature search was conducted via Medline (OVID and PubMed), Scopus, Embase, and Web of Science. Studies that were in English, included intracranial hemangioblastomas treated with preoperative embolization and provided sufficient disaggregated clinical data for each patient were included. Historical control patients with non-embolized intracranial HB undergoing resection were similarly identified. RESULTS: A total of 111 patients that underwent preoperative embolization of HB prior to planned resection were identified. Patient age ranged from 12 to 72 years, with a cohort of 63% males and 36% females. Nine studies comprising 392 non-embolized patients were included as controls. Gross total resection was achieved in 83.7% of embolized and 95.6% of non-embolized patients. Intraoperative blood transfusion was required in 15.3% of embolized and 0.51% of non-embolized controls, while rates of post-operative hemorrhage were 8.4% and 1.6%, respectively. Complication rates from embolization were 11.7% and following consequent surgery were 20.7%. DISCUSSION: Embolization did not increase rates of gross total resection, decrease estimated blood loss, or decrease incidence of complications. Not only does embolization fail to mitigate surgical risks, the embolization procedure itself carries significant risk for complications. Embolization should not be standard of care for intracranial HB.

The kynurenine to tryptophan ratio as a prognostic tool for glioblastoma patients enrolling in immunotherapy.

We hypothesized that peripheral tryptophan (Trp) and/or kynurenine (Kyn) levels would provide prognostic value for physicians planning to enroll glioblastoma multiforme (GBM) patients in immunotherapy. GBM is the most common form of malignant glioma in adults. Despite aggressive surgical resection, irradiation and chemotherapy, patients with GBM have a median survival of only 14.6 months after diagnosis. This poor outcome has led to the search for more effective treatments, including immunotherapy. However, the identification of parameters that proactively stratify GBM patients who have the potential for therapeutic benefit has been challenging. Given recent observations demonstrating high indoleamine 2,3 dioxygenase 1 (IDO1) expression in GBM, the immunosuppressive impact of IDO1-mediated Trp catabolism, as well as active transport of Trp and the IDO1-downstream Trp catabolite, Kyn, across the blood brain barrier, we hypothesized that peripheral blood analysis of this pathway would provide diagnostic utility. When comparing individuals without tumors to GBM patients prior to surgical resection, or at the 48 hour (48 h) and ⩾10 week (10 w+) postoperative time points, Trp levels were significantly decreased (p<0.0002). Similarly, Kyn levels were decreased in the pre- and 48 h postoperative GBM patients (p<0.0001), while there was no difference between individuals without tumors and 10 w+ GBM patients. Interestingly, those 10 w+ patients with a high Kyn/Trp ratio (⩾9.5) had a mean overall survival (OS) of 23.6 ± a standard error of 6.8 months, compared to an OS of 38.7 ± 4.9 months for patients with lower Kyn/Trp values. Since the 10 w+ blood draw and analyses occurred prior to patient enrollment in the heat shock protein peptide complex-96 clinical trial, these novel data suggest that the late Kyn/Trp index may be a relevant clinical benchmark, providing prognostic value for GBM patients who are enrolled in immunotherapeutic regimens.

Self-association behavior of a novel nonproteinogenic ß-strand-mimic in an organic solvent.

The self-association behavior of a newly characterized ß-strand-mimic, presented by an achiral nonproteinogenic model system Boc-γ-Abz-NHMe (1: Boc = tert-butyloxycarbonyl; γ-Abz = γ-aminobenzoic acid; NHMe = N-methylamide), have been investigated using (1)H NMR and FT-IR absorption spectroscopy, in combination with computational ab initio calculations. The concentration dependence of (1)H NMR chemical shifts of the amide-NHs in CDCl3 exhibited noncooperative behavior of self-association, whereas the variable temperature (1)H NMR chemical shifts data of the amide-NHs, i.e., temperature-coefficient (Δδ/ΔT) values, could be accounted for by significant enhancement of self-association, i.e., aggregates higher than dimers. In the absence of N-H···O intramolecular H-bond in 1, the intense FT-IR absorption bands in informative amide-A region, i.e., N-H stretches at ∼3465 and 3438 cm(-1) in chloroform solution, could be interpreted in terms of intermolecular H-bonding. The ab initio quantum mechanical calculations performed on two discrete isolated antiparallel H-bonded duplexes with a face-to-face and an edge-to-edge aromatic-aromatic interaction provided strong support for their relative importance to stabilize favorable dimeric structures. The thermodynamic parameters deduced from van't Hoff plots, constructed from variable temperature (1)H NMR data of the amide-NHs in CDCl3, also substantiated the effectiveness of aromatic-aromatic interactions for dimer formation and higher-order self-association. In view of the enormous structural importance of ß-strand-like building blocks in peptide design, we highlight intrinsic self-associating potentials of the readily available γ-Abz moiety, besides the fact that such planar secondary structural mimics are presumed to offer greater prospective for constructing peptidomimetics and therapeutically relevant small molecules.

Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial.

BACKGROUND: Outcomes for patients with recurrent glioblastoma multiforme (GBM) are poor and may be improved by immunotherapy. We investigated the safety and efficacy of an autologous heat-shock protein peptide complex-96 (HSPPC-96) vaccine for patients with recurrent GBM. METHODS: In this open-label, single-arm, phase II study, adult patients with surgically resectable recurrent GBM were given vaccine after gross total resection. The primary endpoint was overall survival at 6 months. Secondary endpoints included overall survival, progression-free survival, safety, and immune profiling. Outcome analyses were performed in the intention-to-treat and efficacy populations. RESULTS: Between October 3, 2007 and October 24, 2011, 41 patients underwent gross total resection of recurrent GBM and received a median of 6 doses of HSPPC-96 vaccine. Following treatment, 90.2% of patients were alive at 6 months (95% confidence interval [CI]: 75.9-96.8) and 29.3% were alive at 12 months (95% CI: 16.6-45.7). Median overall survival was 42.6 weeks (95% CI: 34.7-50.5). Twenty-seven (66%) patients were lymphopenic prior to therapy, and patients with lymphocyte counts below the cohort median demonstrated decreased overall survival (hazard ratio: 4.0; 95% CI: 1.4-11.8; P = .012). There were no treatment-related deaths. There were 37 serious (grades 3-5) adverse events reported, with 17 attributable to surgical resection and a single grade 3 constitutional event related to the vaccine. CONCLUSION: The HSPPC-96 vaccine is safe and warrants further study of efficacy for the treatment of recurrent GBM. Significant pretreatment lymphopenia may impact the outcomes of immunotherapy and deserves additional investigation.