Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆.

BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.

Outcomes with durvalumab by tumour PD-L1 expression in unresectable, stage III non-small-cell lung cancer in the PACIFIC trial.

BACKGROUND: In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression. PATIENTS AND METHODS: Patients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg every 2 weeks or placebo ≤12 months, stratified by age, sex, and smoking history, but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post hoc (1%) TC cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan-Meier-estimated medians). RESULTS: In total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 35%, 65%, 67%, 33%, and 32% had TC ≥25%, <25%, ≥1%, <1%, and 1%-24%, respectively. As of 31 January 2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (CI); medians]: TC ≥25% (0.41, 0.26-0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43-0.82; 16.9 versus 6.9 months), ≥1% (0.46, 0.33-0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48-1.11; 10.7 versus 5.6 months), 1%-24% [0.49, 0.30-0.80; not reached (NR) versus 9.0 months], and unknown (0.59, 0.42-0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31 January 2019 data cut-off; HR, 95% CI; medians): TC ≥ 25% (0.50, 0.30-0.83; NR versus 21.1 months), <25% (0.89, 0.63-1.25; 39.7 versus 37.4 months), ≥1% (0.59, 0.41-0.83; NR versus 29.6 months), 1%-24% (0.67, 0.41-1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43-0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71-1.84; 33.1 versus 45.6 months). Safety was similar across subgroups. CONCLUSIONS: PFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.

Sweat sodium loss influences serum sodium concentration in a marathon.

The aim of this investigation was to determine the influence of sweat electrolyte concentration on body water and electrolyte homeostasis during a marathon. Fifty-one runners completed a marathon race in a warm and dry environment (24.4 ± 3.6 °C). Runners were classified as low-salt sweaters (n = 21; <30 mmol/L of sweat Na+ concentration), typical sweaters (n = 20; ≥30 and <60 mmol/L of sweat Na+ concentration), and salty sweaters (n = 10; ≥60 mmol/L of sweat Na+ concentration). Before and after the race, body mass and a sample of venous blood were obtained. During the race, sweat samples were collected by using sweat patches, and fluid and electrolyte intake were recorded by using self-reported questionnaires. Low-salt, typical and salty sweaters presented similar sweat rates (0.93 ± 0.2, 0.92 ± 0.29, 0.99 ± 0.21 L/h, respectively), body mass changes (-3.0 ± 1.0, -3.3 ± 1.0, -3.2 ± 0.8%), total Na+ intake (12.7 ± 8.1, 11.5 ± 9.7, 14.5 ± 16.6 mmol), and fluid intake (1.3 ± 0.8, 1.2 ± 0.8, 1.2 ± 0.6 L) during the race. However, salty sweaters presented lower post-race serum Na+ concentration (140.8 ± 1.3 vs 142.5 ± 1.1, 142.4 ± 1.4 mmol/L; P < 0.01) and serum osmolality (297 ± 6 vs 299 ± 5, 301 ± 6 mOsm/kg; P < 0.05) than low-salt and typical sweaters. Sweat electrolyte concentration could influence post-race serum electrolyte concentration in the marathon. However, even the saltiest sweaters did not develop exercise-associated hyponatremia or associated symptoms.

CFTR genotype-related body water and electrolyte balance during a marathon.

The aim of this investigation was to determine the influence of CFTR genotype on body water and electrolyte balance during a marathon. Fifty-one experienced runners completed a marathon race. Before and after the race, body mass and a sample of venous blood were obtained. During the race, sweat samples were collected using sweat patches, and fluid and electrolyte intake were obtained using self-reported questionnaires. Thirty-eight participants (74.5% of the total) were 7T/7T homozygotes, 11 (21.6%) were 7T/9T heterozygotes, and one participant presented the rare genotype 5T/7T. Another participant with 9T/9T presented the mutation p.L206W. Participants with 7T/7T showed higher sweat sodium concentrations (42.2 ± 21.6 mmol/L) than 7T/9T (29.0 ± 24.7 mmol/L; P = 0.04). The runner with the 5T/7T genotype (10.2 mmol/L) and the participant with the p.L206W mutation (20.5 mmol/L) exhibited low-range sweat sodium concentrations. However, post-race serum sodium concentration was similar in 7T/7T and 7T/9T (142.1 ± 1.3 and 142.4 ± 1.6 mmol/L, respectively; P = 0.27) and did not show abnormalities in participants with the 5T/7T genotype (140.0 mmol/L) and the p.L206W mutation (143.0 mmol/L). Runners with the CFTR-7T/7T genotype exhibited increased sweat sodium concentrations during a marathon. However, this phenotype was not related with increased likelihood of suffering body water and electrolyte imbalances during real competitions.

Effects of oral salt supplementation on physical performance during a half-ironman: A randomized controlled trial.

The aim of this study was to investigate the effectiveness of oral salt supplementation to improve exercise performance during a half-ironman triathlon. Twenty-six experienced triathletes were matched for age, anthropometric data, and training status, and randomly placed into the salt group (113 mmol Na(+) and 112 mmol Cl(-)) or the control group (cellulose). The experimental treatments were ingested before and during a real half-ironman triathlon competition. Pre- and post-race body mass, maximal force during a whole-body isometric strength test, maximal height during a countermovement jump, were measured, and blood samples were obtained. Sweat samples were obtained during the running section. Total race time was lower in the salt group than in the control group (P = 0.04). After the race, whole-body isometric strength (P = 0.17) and jump height (P = 0.49) were similarly reduced in both groups. Sweat loss (P = 0.98) and sweat Na(+) concentration (P = 0.72) were similar between groups. However, body mass tended to be less reduced in the salt group than in the control group (P = 0.09) while post-race serum Na(+) (P = 0.03) and Cl(-) (P = 0.03) concentrations were higher in the salt group than in the control group. Oral salt supplementation was effective to lessen body mass loss and increase serum electrolyte concentration during a real half-ironman.

Laparoscopic adrenalectomy for large adrenal masses: a challenge or a routine?

AIM: The increased incidence of malignancy and the concern for higher rate of complications with laparoscopic resection of larger tumors typically limits laparoscopic adrenalectomy to small adrenal masses. We used our prospectively collected database to compare laparoscopic adrenalectomy outcomes between small and large adrenal tumors. METHODS: Operative details and outcomes were compared by adrenal mass size size: Group A≤4 cm and Group B>4 cm, for consecutive laparoscopic adrenalectomies performed between 2009 and 2013. RESULTS: Group A (N.=50) and Group B (N.=27) subjects had similar operative times (131 vs. 132 min, P=0.48). Group B subjects were older, had more adrenal malignancies, and had a higher blood loss with a slightly larger change in hemoglobin than Group A subjects; however, no subject required blood transfusion and complication rates were similar between groups (4% vs. 11%, P=0.34). One subject from each group required conversion to open adrenalectomy. CONCLUSION: Laparoscopic adrenalectomy can be performed safely for adrenal masses >4 cm and size is not a contraindication to the laparoscopic approach.

The Role of Vitamin D in the Treatment of Carpal Tunnel Syndrome: Clinical and Electroneuromyographic Responses.

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.

Viral infections of the central nervous system in Spain: a prospective study.

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.

Theory of the kinetics of luminescence and its temperature dependence for Ag nanoclusters dispersed in a glass host.

We have measured and fitted the kinetics of luminescence of Ag nanoclusters homogeneously dispersed within the bulk of an oxyfluoride glass, with various sample temperatures. The balance equations for the populations of the excited singlet and triplet states of the Ag nanoclusters are proposed and used in this fitting while taking into account inter-system crossing between the singlet and triplet states and their wavelength dependent spontaneous decay to the ground singlet state. The involved energy barriers and rate constants and spontaneous emission cross-sections for the excited singlet and triplet states are evaluated.

Experiment and theoretical modeling of the luminescence of silver nanoclusters dispersed in oxyfluoride glass.

Density functional theory (DFT) and complete active space perturbation theory (CASPT2) have been applied for modeling the configuration, charge, energy states, and spin of luminescent Ag nanoclusters dispersed within the bulk of oxyfluoride glass host. The excitation spectra of luminescence of the Ag nanoclusters have been measured and simulated by means of the DFT and CASPT2. Electron spin resonance spectra have been recorded and suggest diamagnetic state of Ag nanoclusters. The silver nanoclusters have been argued to consist mostly of pairs of Ag(2) (+) dimers, or Ag(4) (2+) tetramers, with different extent of distortion along the tetramer diagonal. The sites for the Ag nanoclusters have been suggested where the pairs of Ag ions substitute onto metal and hole cation sites and are surrounded by fluorine ions within a fluorite-type lattice.

Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial.

BACKGROUND: The phase III PACIFIC trial (NCT02125461) established consolidation durvalumab as standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC) and no disease progression following chemoradiotherapy (CRT). In some cases, patients with stage IIIA-N2 NSCLC are considered operable, but the relative benefit of surgery is unclear. We report a post hoc, exploratory analysis of clinical outcomes in the PACIFIC trial, in patients with or without stage IIIA-N2 NSCLC. MATERIALS AND METHODS: Patients with unresectable, stage III NSCLC and no disease progression after ≥2 cycles of platinum-based, concurrent CRT were randomized 2 : 1 to receive durvalumab (10 mg/kg intravenously; once every 2 weeks for up to 12 months) or placebo, 1-42 days after CRT. The primary endpoints were progression-free survival (PFS; assessed by blinded independent central review according to RECIST version 1.1) and overall survival (OS). Treatment effects within subgroups were estimated by hazard ratios (HRs) from unstratified Cox proportional hazards models. RESULTS: Of 713 randomized patients, 287 (40%) had stage IIIA-N2 disease. Baseline characteristics were similar between patients with and without stage IIIA-N2 NSCLC. With a median follow-up of 14.5 months (range: 0.2-29.9 months), PFS was improved with durvalumab versus placebo in both patients with [HR = 0.46; 95% confidence interval (CI), 0.33-0.65] and without (HR = 0.62; 95% CI 0.48-0.80) stage IIIA-N2 disease. Similarly, with a median follow-up of 25.2 months (range: 0.2-43.1 months), OS was improved with durvalumab versus placebo in patients with (HR = 0.56; 95% CI 0.39-0.79) or without (HR = 0.78; 95% CI 0.57-1.06) stage IIIA-N2 disease. Durvalumab had a manageable safety profile irrespective of stage IIIA-N2 status. CONCLUSIONS: Consistent with the intent-to-treat population, treatment benefits with durvalumab were confirmed in patients with stage IIIA-N2, unresectable NSCLC. Prospective studies are needed to determine the optimal treatment approach for patients who are deemed operable.

Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion.

Cell surface glycosaminoglycans (GAGs) play an important role in the attachment and invasion process of a variety of intracellular pathogens. We have previously demonstrated that heparan sulfate proteoglycans (HSPG) mediate the invasion of trypomastigote forms of Trypanosoma cruzi in cardiomyocytes. Herein, we analysed whether GAGs are also implicated in amastigote invasion. Competition assays with soluble GAGs revealed that treatment of T. cruzi amastigotes with heparin and heparan sulfate leads to a reduction in the infection ratio, achieving 82% and 65% inhibition of invasion, respectively. Other sulfated GAGs, such as chondroitin sulfate, dermatan sulfate and keratan sulfate, had no effect on the invasion process. In addition, a significant decrease in infection occurred after interaction of amastigotes with GAG-deficient Chinese Hamster Ovary (CHO) cells, decreasing from 20% and 28% in wild-type CHO cells to 5% and 9% in the mutant cells after 2 h and 4 h of infection, respectively. These findings suggest that amastigote invasion also involves host cell surface heparan sulfate proteoglycans. The knowledge of the mechanism triggered by heparan sulfate-binding T. cruzi proteins may provide new potential candidates for Chagas disease therapy.

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus.

AIM: To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. METHODS: After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree). Consensus was reached if 2/3 of the participants are in the median range. RESULTS: In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. CONCLUSIONS: A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations.

SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020).

Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

Using the Flipped Classroom Model in Surgical Education: Efficacy and Trainee Perception.

OBJECTIVE: To describe the feasibility, efficacy, and learner perception of the flipped classroom model for teaching conferences within surgical training programs. DESIGN: For the flipped classroom conferences, video lectures were prepared by a faculty member, and sent to all attendees at least 2 days prior to lecture. The conference time was then spent going over cases and questions, rather than traditional lecture. We conducted a qualitative survey to assess learner's perceptions and pre-lecture quizzes to assess trainee preparedness. SETTING: The comparison of pre-conference quizzes between flipped classroom and traditional models was carried out at Brooke Army Medical Center (BAMC) in San Antonio, TX, a tertiary care facility with a general surgery residency program. The survey was conducted at BAMC and within the Complex General Surgical Oncology fellowship program at University of Texas MD Anderson Cancer Center, where a flipped classroom model was similarly employed. PARTICIPANTS: Surgical residents BAMC participated in pre-lecture quizzes. BAMC residents and MD Anderson fellows were invited to complete the online survey. RESULTS: Lecture videos did not increase mean preparation time (1.53 vs. 1.46 hours without vs. with video, p = 0.858), but did increase mean quiz scores from 67% to 80% (p = 0.031) with 32/35 learners utilizing videos. Videos increased the proportion of learners who self-reported preparing at all from 42% to 95% (p = 0.28), and preparing for at least one hour for conference from 23% to 49% (p = 0.014). Of survey respondents, 90% said videos were very helpful, 90% would use them weekly if available, and 90% prefer this format to traditional lecture. CONCLUSIONS: Utilization of a flipped classroom method was well received and preferred by surgical trainees, and it increased performance on pre-conference quizzes without increasing preparation time. Although creation of video lectures is work-intensive for lecturers, these results suggest it is more effective for learner preparation. These results could be generalizable to surgical residents nationwide as technology utilization increases in surgical education.

Human parechoviruses in infants with systemic infection.

Human parechoviruses (HPeVs) are RNA viruses related to neonatal sepsis, meningoencephalitis and other infections in young children. Little clinical and epidemiological information is available on these viruses. HPeVs were sought in cerebrospinal fluid from 397 infants aged less than 12 months from whom a sample was obtained to exclude meningitis or encephalitis from 2006 to 2009. HPeV infections were also tested in stool samples from 271 children aged less than 3 years old with gastroenteritis from November 2008 to March 2009. HPeV detection was by real-time polymerase chain reaction assay (region 5'UTR), followed by genotyping (region VP3/VP1). HPeVs were detected in the cerebrospinal fluid of nine infants (2.3%), one aged 6 months and eight aged 14-55 days old. All were admitted to hospital for febrile syndrome with abrupt clinical deterioration and suspected systemic infection without clear laboratory signs of meningeal inflammation. The same virus was detected in all the available nasopharyngeal aspirates, stool, and/or serum samples from each patient. At least eight of the nine cases were caused by HPeV3. HPeVs were detected in stool samples from 17 children (6.3%), the most prevalent types being types 1 and 3. In conclusion, HPeV infection is common in the Basque Country (Spain) and HPeV3 is a significant cause of hospital admission due to systemic infection in the first few months of life. In these patients, HPeVs should be investigated as part of routine tests for enterovirus.

Morphological and Semi-empirical Study of the Pluronic F68/Imogolite/Sudan III Intersurfaces Composite for the Controlled Temperature Release of Hydrophobic Drugs.

Some PluronicF68 (F68) triblock copolymer properties demonstrate surprising applications in selective drug administration, such as the transportation of hydrophobic anti-inflammatories through epithelial barriers. Nuclear magnetic resonance (1H-NMR) spectroscopy was carried out for micelle precursor dispersions and F68 films modified with a synthetic imogolite (IMO) biocompatible hydrogel. Theoretical calculations and morphological assessment for the process of morphogenesis of dendritic crystallization were performed by molecular docking and atomic force microscopy (AFM) of the Sudan III-IMO-F68 composite, which was more hydrophobic than Sudan III-F68 and carried out the prolonged release of the Sudan III "drug" captured by a water-octanol interface determined by standard absorbance. Surface fusions were measured and compared to the unmodified matrix. However, despite the superior properties of the composite, the critical micelle concentration (CMC) was practically unmodified because solitary IMO strands attached to Sudan III formed Sudan III-IMO. These strands unraveled in a stable manner by expanding like a "spiderweb" in hydrophilic interfaces according to NMR analysis of the hydrogen one H1 polarization of Sudan III and F68 methyl, whose correlation relates hydrophobicity of Sudan III-IMO-F68 with dendrite properties from F68 concentrations. CMC and surface fusions equivalent to F68 surface properties, calculated by differential scanning calorimetry and dynamic Raman spectroscopy, were determined by AFM and high-resolution ellipsometry. Our results show highly specialized pharmacological applications since micelle surfaces expand, triggering maximum deliveries of "Drugs" from its interior to the physiological environment. The implanted sensor prototype determined equilibria reached Sudan III according to temperature (32-50 °C) and time it took to cross the membrane model 1-octanol (48 h). The findings suggest that the targested design of a F68-IMO-"Drug" would function as a microdevice for the prolonged release of hydrophobic drugs. In addition, the said microdevice could regenerate the damaged tissue in the central nervous system or other organs of the body. This is due to the fact that it could perform both tasks simultaneously, given the properties and characteristics acquired by the compatible material depending on the temperature of the physiological environment.

Pathogen associated molecular pattern-decorated mesoporous silica-A colloidal model for studying bacterial-host cell interactions.

Tuberculosis is the top infectious disease worldwide and the development of a vaccine and diagnostic tools to control the disease is a priority that requires a better understanding of the factors involved in the pathogenesis of Mycobacterium tuberculosis, the infectious agent. It is known that bacterial cell surface components are released, interact with immune cell receptors, and may traffic toward host cell structures. Many of these compounds are lipids that have been associated with mycobacterial virulence. However, their hydrophobic nature has frequently hampered their biological study. In this work, silica particles were coated with functional lipids to obtain a colloidal bioinspired system based on nonhydrosoluble glycolipids. Mycobacterium tuberculosis phosphatidylinositol mannosides (PIMs), known to interact with receptors of innate immune cells, were purified from the M. tuberculosis H37Rv type strain, and used to prepare large unilamellar liposomes in combination with zwitterionic phosphatidyl choline. Then, bacillary-like Santa Barbara Amorphous-15 (SBA-15) silica particles were cationized and the vesicle fusion method was used to promote the attachment of anionic PIM-containing lipid bilayers. Thermogravimetric analysis, x-ray diffraction, N2 adsorption-desorption isotherm analysis, Fourier transform infrared spectroscopy, electron microscopy, and zeta potential analyses were used to characterize the materials obtained. The as-prepared PIM-containing colloids, named PIM@SBA-15, showed biocompatibility toward human fibroblasts and were found to colocalize with Toll-like receptor (TLR)2 upon their incubation with THP1-derived macrophages. Furthermore, the particles induced the formation of pseudopods and were internalized into phagocytic cells. In all, these data suggest the usefulness of PIM@SBA-15 particles to better comprehend the interactions between immune cells and PIMs.

Diffuse reflectance spectroscopy characterization of hemoglobin and intralipid solutions: in vitro measurements with continuous variation of absorption and scattering.

Absorption and scattering processes in biological tissues are studied through reflectance spectroscopy in tissue-like phantoms. For this aim, an experimental setup is designed to independently control both processes in hemoglobin and intralipid solutions. From the analysis of the obtained spectra, a simple empirical power law equation is found that relates absorbance with scattering and absorption coefficients. This relationship includes three wavelength independent parameters, which can be determined geometry from in vitro measurements for each particular optical optode. The dependence of the optical path length on the absorption and scattering coefficients is also analyzed, and estimations of this parameter for physiological conditions are presented. This study is useful to better understand the scattering phenomena in biological tissue, and to obtain absolute concentration of absorber particles when a homogeneous medium can be assumed.