Microsphere-based scaffolds for cartilage tissue engineering: Using subcritical CO2 as a sintering agent

Shape-specific, macroporous tissue engineering scaffolds were fabricated and homogeneously seeded with cells in a single step. This method brings together CO₂ polymer processing and microparticle-based scaffolds in a manner that allows each to solve the key limitation of the other. Specifically, microparticle-based scaffolds have suffered from the limitation that conventional microsphere sintering methods (e.g., heat, solvents) are not cytocompatible, yet we have shown that cell viability was sustained with subcritical (i.e., gaseous) CO₂ sintering of microspheres in the presence of cells at near-ambient temperatures. On the other hand, the fused microspheres provided the pore interconnectivity that has eluded supercritical CO₂ foaming approaches. Here, fused poly(lactide-co-glycolide) microsphere scaffolds were seeded with human umbilical cord mesenchymal stromal cells to demonstrate the feasibility of utilizing these matrices for cartilage regeneration. We also demonstrated that the approach may be modified to produce thin cell-loaded patches as a promising alternative for skin tissue engineering applications.     

Strategies for successful aging

As a nation we are getting older and not all individuals will be fortunate enough to age as successfully as Jean Calment. Improving governmental policies and improving dissemination of information regarding aging to the lay public and health care professionals can make a difference though in how many older individuals can achieve old age with less disability. Teamwork among the patient, health care professionals, and society as a whole can help burnish the "golden years."     

Norfloxacin and cisapride combination decreases the incidence of spontaneous bacterial peritonitis in cirrhotic ascites

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis with ascites, having high recurrence despite antibiotic prophylaxis. Small bowel dysmotility and bacterial overgrowth have been documented to be related to SBP. The purpose of the present paper was (i) to study whether addition of a prokinetic agent to norfloxacin ameliorates the development of SBP in high-risk patients; and (ii) to identify risk factors for SBP development. METHODS: A prospective, single blinded, randomized controlled trial was conducted in high-risk cirrhotic patients with ascites who had either recovered from an episode of SBP or who had low ascitic fluid protein. Norfloxacin 400 mg once daily (group I) or norfloxacin 400 mg once daily with cisapride 20 mg twice a day (group II) was given and occurrence of side-effects of therapy and mortality were recorded. RESULTS: Of the 94 patients, 48 (51%) were in group I, and 46 (49%) in group II. The actuarial probability of developing SBP at 12 month in group I was 56.8% and in group II, 21.7% (P = 0.026). Treatment failure was observed in five patients (10%) in group I and none in group II (P = 0.003). The actuarial probability of death at 18 months was 20.6% in group I and 6.2% in group II (P = 0.1). Low serum albumin, low ascitic fluid protein and alcoholic cirrhosis were related to development of SBP (P < 0.05). Additionally, low serum albumin (2.8 g/dL), gastrointestinal bleeding, alcoholic cirrhosis and low ascitic fluid protein were significantly associated with multiple occurrences of SBP. CONCLUSIONS: Prophylaxis with norfloxacin and cisapride significantly reduces the incidence of SBP in high-risk cirrhosis patients; low serum albumin, low ascitic fluid protein and alcoholic cirrhosis predispose to the development of SBP in high-risk cirrhosis patients; and low ascitic fluid protein should also be considered as a risk factor for the development of SBP requiring prophylaxis.     

Prevalence of pulmonary nocardiosis in a tuberculosis hospital in Amritsar, Punjab

The prevalence of pulmonary nocardiosis in a tuberculosis and chest diseases hospital in Amritsar is reported. Of 1510 sputum samples cultured from 1016 patients, 67 sputa originating from 16 patients were found to be positive for the Nocardia asteroides species complex. Based upon repeated isolation of N. asteroides from the respiratory tract, its microscopic demonstration in KOH wet mounts or stained smears of sputum and clinical evaluation of patients, 14 cases of pulmonary nocardiosis were diagnosed. This gave a prevalence of 1.4% pulmonary nocardiosis in the tuberculosis hospital. The prevalence of the disease was found to be 1.3% in the males as against 1.5% in the females. Of the various clinical categories of patients investigated, pulmonary tuberculosis with sputum negative for acid-fast bacilli (AFB) yielded the highest prevalence of 3.2%, followed by 1.3%, 1.2%, 1.1% and 0.5% in pneumonia, chronic obstructive pulmonary disease (COPD), bronchiectasis and pulmonary tuberculosis with sputum positive for AFB, respectively. Type IV cutaneous hypersensitivity to nocardin was observed in 19 of 908 (2%) patients tested, whereas only a solitary positive reactor was found among 260 healthy volunteers. Twelve of 19 nocardin positive reactors (63%) had unequivocally proven pulmonary nocardiosis. The nocardin skin test gave false negative results in two nocardiosis patients. More comprehensive investigations are warranted in order to evaluate the nocardin skin test as an additional aid for the diagnosis of nocardiosis. Barring a solitary exception, the nocardiosis patients were successfully treated with sulphadiazine or trimethoprim-sulphamethoxazole (TMP-SMZ) combination. To the best of our knowledge, this is the largest series of pulmonary nocardiosis patients in a prospective study as yet reported from India. The observations underscore the point that nocardiosis warrants greater attention in the differential diagnosis of bronchopulmonary diseases.     

Dysregulation of the epigenome in triple-negative breast cancers: Basal-like and claudin-low breast cancers express aberrant DNA hypermethylation

A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers. The breast cancers that express this gene expression signature are enriched for triple-negative subtypes — basal-like and claudin-low breast cancers. Methylation analysis of primary breast cancers showed extensive promoter hypermethylation of epigenetic biomarker genes among triple-negative breast cancers, compared to other breast cancer subclasses where promoter hypermethylation events were less frequent. Furthermore, triple-negative breast cancers either did not express or expressed significantly reduced levels of protein corresponding to methylation-sensitive biomarker gene products. Together, these findings suggest strongly that loss of epigenetic biomarker gene expression is frequently associated with gene promoter hypermethylation events. We propose that aberrant DNA hypermethylation is a common characteristic of triple-negative breast cancers and may represent a fundamental biological property of basal-like and claudin-low breast cancers. Kaplan–Meier analysis of relapse-free survival revealed a survival disadvantage for patients with breast cancers that exhibit aberrant DNA hypermethylation. Identification of this distinguishing trait among triple-negative breast cancers forms the basis for development of new rational therapies that target the epigenome in patients with basal-like and claudin-low breast cancers.     

Use of Intravenous Thrombolysis in Acute Ischemic Stroke Management in Patients with Active Malignancies: A Topical Review

ObjectivesOur review aims to present existing data on the safety of Intravenous thrombolysis (IVT) use in acute ischemic stroke (AIS) patients with concomitant central nervous system or systemic malignancies, with attention to special circumstances pertaining to specific cancer subtypes to help in acute decision making, especially for neurologists and emergency medicine physicians.MethodsA literature search was conducted on electronic databases inclusive of Medline, EMBASE and CINAHL for articles published or available in English between January 1, 2000 to June 1, 2020 using the following search terms: “acute ischemic stroke,” “cerebrovascular disease,” “Intravenous thrombolysis,” “tissue plasminogen activator,” “cancer patients,” and “neoplasm”.ConclusionRecognition of stroke symptoms in patients with active cancer, in particularly those involving the brain, requires astute clinical judgement. Decision-making can be improved by understanding baseline functional status, cancer prognosis and expected disability from stroke, as well as utilizing diagnostic modalities such acute MRI where needed. While this article does not encourage use of IVT in patients with all malignancies, it lays the groundwork for decision making should thrombolysis be a consideration in a patient with AIS in a cancer patient.     

Delayed presentation of a large congenital laryngeal cleft in an adult

Laryngeal clefts are rare congenital malformations of the posterior laryngotracheal wall that lead to an abnormal communication between the airway and pharyngo-oesophageal tract. The condition is almost universally identified during infancy with minor laryngeal clefts very rarely diagnosed in adulthood. We present our tertiary centre’s experience of a large laryngeal cleft presenting at an advanced age, with the aim of increasing awareness of this correctible cause of respiratory distress and aspiration in adults.