Biophysical investigation of liposome systems decorated with bioconjugated copolymers in the presence of amantadine.

Liposome-based technologies derived from lipids and polymers (e.g., PEGylated liposomes) have been recognized because of their applications in nanomedicine. However, since such systems represent myriad challenges and may promote immune responses, investigation of new biomaterials is mandatory. Here, we report on a biophysical investigation of liposomes decorated with bioconjugated copolymers in the presence (or absence) of amantadine (an antiviral medication). First, copolymers of poly(N,N-dimethylacrylamide-co-fluoresceinacrylate-co-acrylic acid-N-succinimide ester)-block-poly(N-isopropylacrylamide) (PDMA-b-PNIPAM) containing a fluorescence label were biofunctionalized with short peptides that resemble the sequence of the loops 220 and 130 of the binding receptor of the hemagglutinin (HA) protein of the influenza A virus. Then, the bioconjugated copolymers were self-assembled along with liposomes composed of 1,2 dimyristoyl-sn-glycero-3-phosphocholine, sphingomyelin, and cholesterol (MSC). These biohybrid systems, with and without amantadine, were systematically characterized using differential scanning calorimetry (DSC), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryoTEM). Finally, the systems were tested in an in vitro study to evaluate cytotoxicity and direct immunofluorescence in Madin Darbin Canine Kidney (MDCK) cells. The biohybrid systems displayed long-term stability, thermo-responsiveness, hydrophilic-hydrophobic features, and fluorescence properties and were presumable endowed with cell targeting properties intrinsically integrated into the amino acid sequences of the utilized peptides, which indeed turn them into promising nanodevices for biomedical applications.

Differential impact on motor unit characteristics across severities of adult spinal muscular atrophy.

OBJECTIVE: To test the hypotheses that decomposition electromyography (dEMG) motor unit action potential (MUAP) amplitude and firing rate are altered in SMA; dEMG parameters are associated with strength and function; dEMG parameters are correlated with traditional electrophysiological assessments. METHODS: Ambulatory and non-ambulatory adults with SMA on nusinersen and healthy controls were enrolled. MUAPs were decomposed from multielectrode surface recordings during 30-s maximum contraction of the abductor digiti minimi (ADM). Isometric strength, upper limb function, patient-reported function, and standard electrophysiologic measures of the ADM (compound muscle action potential [CMAP], single motor unit potential [SMUP], motor unit number estimation [MUNE]) were collected. RESULTS: dEMG MUAP amplitudes were higher in ambulatory versus control and non-ambulatory groups and were higher in controls versus non-ambulatory SMA. In contrast, dEMG firing rates were higher in ambulatory versus non-ambulatory and control groups but similar between non-ambulatory and control. dEMG parameters showed moderate to strong positive correlation with strength and function whereas CMAP and MUNE better correlated with function than strength. SMUP did not correlate with strength, function, or dEMG MUAP amplitude. dEMG parameters show overall good test-retest reliability. INTERPRETATION: dEMG provided reliable, noninvasive measure of MUAP amplitude size and firing rate and revealed divergent patterns across disease severity in adults with SMA. Firing rate enhancement, as seen in milder SMA, may provide a therapeutic avenue for improving function in more severe SMA, where firing rates appear preserved. MUAP amplitude size and firing rate, quantified with dEMG, may be promising monitoring biomarker candidates for noninvasive assessment of SMA.

[Gallstone ileus, experience in the Dr. Eduardo Liceaga General Hospital of Mexico]. / Íleo biliar, experiencia en el Hospital General de México Dr. Eduardo Liceaga.

BACKGROUND: Gallstone ileus is a rare cause of intestinal obstruction (1-4%). It results from the migration of a gallstone through a bilio-enteric fistula. Treatment begins with fluid therapy, followed by enterolithotomy, fistula closure, and cholecystectomy. OBJECTIVES: To determine the clinical presentation in patients with gallstone ileus and subsequent medical -surgical management outcomes. MATERIAL AND METHODS: A retrospective, observational, descriptive and transversal study was conducted on patients diagnosed with intestinal obstruction secondary to a gallstone ileus from May 2013 to October 2014. The following variables were recorded: age, sex, comorbidities, mean time of onset of symptoms, length of preoperative and postoperative stay, imaging studies, biochemical tests, type of surgical management, stone location and size, complications, mortality, and postoperative follow-up. RESULTS: The study included 10 patients (male: female ratio 1:4), with a mean age of 61.9 years. The mean time of onset symptoms 15.4 days, and preoperative stay was 2days. On admission, 80% of patients had leukocytosis and neutrophilia, and 70% with renal failure. The most common surgical management was enterolithotomy with primary closure (50%), finding 80% of the stones in the terminal ileum. Recurrence was found in 2 cases. Mean postoperative hospital stay was 6.3 days. Mortality was 20%. CONCLUSIONS: Gallstone ileus most commonly presented in women in the seventh decade of life, with intermittent bowel obstruction. On hospital admission, they presented with systemic inflammatory response, electrolyte imbalance and abnormal liver function tests. Initial treatment must include fluid-electrolyte replacement, and tomography scans must be made in all cases. In our experience, the best procedure is enterolithotomy and primary closure, which presented lower morbidity and mortality.