Irritable Bowel Syndrome Patients’ Ideal Expectations and Recent Experiences with Healthcare Providers: A National Survey

The purpose of this paper is to identify patients’ ideal expectations from their healthcare providers. The IBS-Patient Education Questionnaire was developed using focus groups, and was administered to a national sample of IBS patients. Frequencies of item endorsements were obtained. Subgroup analysis was done comparing the responses for patients’ ideal expectations of their healthcare providers vs. their experiences with their last provider. Among the 1,242 patients who completed the survey, the mean age was 39.3 years, educational attainment 15 years, 85% female, IBS duration 6.9 years, 1,028 (83%) had seen a physician for IBS in the past, and 92.6% have used the Internet to obtain health information. Among the subjects who have seen a physician for IBS, the most desired qualities of providers were to give comprehensive information (96%), to refer to a source for additional information (95.8%), to answer questions (95.9%), to listen (94.4%), to provide information about IBS studies and medications (94%), and to provide support (88.6%) and hope (82.1%). Importantly, patients’ prior experiences with their last healthcare provider differed from their ideal expectations: “provide information” (38.3%); answer questions during the visit (68%), “to listen” (63.8%), and support (47.1%). Patients’ ideal expectations from healthcare providers (what patients ideally would like to experience) relate to obtaining information and relationship needs of receiving support and hope. Notably, their prior experiences with recent healthcare providers (what patients perceived actually occurred) were different from their ideal expectations. A better understanding of different types of expectations is necessary in order to construct an effective therapeutic relationship, which is critical for the management of IBS. Practice implications: Practice guidelines for IBS should emphasize a better understanding of a patient’s expectations and the therapeutic value of patient–provider communication.     

Early Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus

Childhood maltreatment represents a major risk factor for the development of numerous childhood psychopathologies that in many cases linger as chronic mental illnesses in adulthood. Exposing rodents or non-human primates to early life stress increases anxiety-like behaviors and impairs cognitive function in adulthood, suggesting that animal models may provide important insights into parallel developmental processes in humans. Using an unbiased genomic screen, we found that expression of lipopolysaccharide binding protein (LBP), a member of the innate immune system, is dramatically decreased in the hippocampus of pups exposed to early life stress. LBP levels peak in the normally developing hippocampus at a period of intense synaptic pruning, during which LBP is colocalized with the synaptic marker PSD95 and is found in close proximity to processes of microglia cells. Expression of LBP declines to low levels seen in adulthood at around postnatal day 30. Importantly, 30-day-old LBP knockout (k.o.) mice show increased spine density and abnormal spine morphology, suggesting that peak levels of LBP during the second and third weeks of life are necessary for normal synaptic pruning in the hippocampus. Finally, LBP k.o. mice show impaired hippocampal-dependent memory and increased anxiety-like behaviors in a manner that resembles that seen in animals exposed to early life stress. These findings describe a novel role for LBP in normal hippocampal development and raise the possibility that at least some of the behavioral sequelae of early life stress are mediated by reduced expression of LBP during a critical period of neurodevelopment.     

Discovery of small molecule inhibitors that interact with γ-tubulin

Recent studies have shown an overexpression of γ-tubulin in human glioblastomas and glioblastoma cell lines. As the 2-year survival rate for glioblastoma is very poor, potential benefit exists for discovering novel chemotherapeutic agents that can inhibit γ-tubulin, which is known to form a ring complex that acts as a microtubule nucleation center. We present experimental evidence that colchicine and combretastatin A-4 bind to γ-tubulin, which are to our knowledge the first drug-like compounds known to interact with γ-tubulin. Molecular dynamics simulations and docking studies were used to analyze the hypothesized γ-tubulin binding domain of these compounds. The suitability of the potential binding modes was evaluated and suggests the subsequent rational design of novel targeted inhibitors of γ-tubulin.     

Submitral aneurysmorraphy with mitral valve replacement — A case report

Submitral left ventricular aneurysm is a rare complex disorder, predominently found in African population. We report a case of a 45 year male diagnosed to have a large submitral aneurysm, eroding the left circumflex artery, leading to severe mitral regurgitation, severe tricuspid regurgitation and congestive heart failure. Surgical correction comprising of submitral aneurysmorraphy with Teflon Felt, mitral valve replacement, modified DeVega’s tricuspid annuloplasty and ligation of left distal circumflex was performed successfully in this case.     

Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK

Curcumin, a major active component of turmeric, is known to induce apoptosis in several types of cancer cells, but little is known about its activity in chemoresistant cells. Hence, the aim of the present study was to investigate the anticancer properties of curcumin in cisplatin-resistant human ovarian cancer cells in vitro. The results indicated that curcumin inhibited the proliferation of both cisplatin-resistant (CR) and sensitive (CS) human ovarian cancer cells almost equally. Enhanced superoxide generation was observed in both CR and CS cells treated with curcumin. Curcumin induced G(2)/M phase cell-cycle arrest in CR cells by enhancing the p53 phosphorylation and apoptosis through the activation of caspase-3 followed by PARP degradation. Curcumin also inhibited the phosphorylation of Akt while the phosphorylation of p38 MAPK was enhanced. In summary, our results showed that curcumin inhibits the proliferation of cisplatin-resistant ovarian cancer cells through the induction of superoxide generation, G(2)/M arrest, and apoptosis.     

Prospective, Longitudinal Study of Plastic Bronchitis Cast Pathology and Responsiveness to Tissue Plasminogen Activator

Plastic bronchitis (PB) is a rare disease that often occurs in patients with congenital heart disease (CHD) who have undergone staged single-ventricle palliation. It is characterized by the formation of rubbery “casts” in the airways. PB treatment frequently includes inhaled tissue plasminogen activator (tPA). However, the efficacy of tPA to reduce cast burden is unknown. This is further complicated by our lack of knowledge of cast composition. We obtained spontaneously expectorated PB casts from children (n = 4) with CHD and one adult patient with idiopathic PB. Pathological assessment was made from paraffin-preserved samples. Casts were treated with phosphate-buffered saline (PBS) or tPA. Cast response to tPA was assessed by changes in cast weight and the production of fibrin d-dimer. Independent of dose, tPA reduced cast weight compared with PBS-treatment (P = 0.001) and increased d-dimer levels. Histological staining showed that PB casts from all patients were composed of fibrin and contained notable numbers of lymphocytes. Cast composition did not change over time. Collectively, these data support that in our PB patients, casts are composed of fibrin and are responsive to tPA treatment. This makes inhaled tPA a potentially viable option for symptomatic relief of PB while we work to unravel the complexity of PB pathogenesis.