A systematic narrative synthesis of acute amplification-induced improvements in cognitive ability in hearing-impaired adults

Objective: This systematic review investigated if hearing aid use was associated with acute improvements in cognitive function in hearing-impaired adults.

Design: The review question and inclusion/exclusion criteria were designed using the Population, Intervention, Control, Outcomes, and Study design (PICOS) mnemonic. The review was pre-registered in the International Prospective Register of Systematic Review (PROSPERO) and performed in accordance with the statement on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Study sample: Thirteen articles, of various designs, published between 1990 and 2018, were identified via a search of five electronic databases.

Results: Most studies reported 1–2 cognitive outcome measures. Nine studies reported a significant improvement in outcome and four studies reported no significant change. None of the 13 studies received a high score on a quality assessment checklist. Due to concerns over risk of bias and indirectness, the overall quality of evidence was graded as low.

Conclusions: Only a few studies were identified, some of which report a small improvement in cognitive outcome; however, the overall quality of evidence was low. Further research is very likely to have an important impact on our confidence in answering the review question.     

Papillary fibroelastoma of the tricuspid valve presenting as neonatal pulmonary haemorrhage

Papillary fibroelastoma is a benign tumour of the cardiac valve apparatus. We present an unusual case of life-threatening pulmonary haemorrhage and disseminated intravascular coagulation in a neonate associated with this benign cardiac tumour. Papillary fibroelastoma of the tricuspid valve rarely presents in children and, to our knowledge, this is only the second reported case in a neonate. The patient was successfully managed by anticoagulation therapy followed by surgical excision of the tumour. This case illustrates the potentially fatal presentation of this benign cardiac tumour among neonates. Conclusion: Pulmonary haemorrhage of this degree is unusual in an otherwise healthy term neonate and needs careful investigation for unusual pathology including potential sources of pulmonary emboli in the heart. We emphasize the value of echocardiography in the evaluation of unexpected pulmonary haemorrhage in the newborn.     

A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic colorectal cancer

The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation Program, National Cancer Institute) has broad preclinical anti-neoplastic activity. Preliminary data from phase I study demonstrated anti-tumor activity in colorectal carcinoma. This phase II trial evaluates its efficacy in patients with minimally treated metastatic colorectal cancer. Eligibility included Karnofsky performance status 70%, age 18 years and bidimensionally measurable disease. Thirteen patients were treated with NSC 655649 at 500mg/m² by central venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median [range] 2 [1–6]) of therapy were administered. Twelve patients are eligible for response assessment. No major objective responses were seen using the RECIST criteria; however stable disease was observed in three patients with mean duration of 15 weeks. The median time to progression was 8 weeks. There was no toxic death. Four patients received only one cycle of treatment, and three had disease progression. Toxicities were tolerable and hematologic toxicity was the most common. The median (range) granulocyte and platelet nadir counts were 2043/l (116–16,374/l) and 276×10³/l (5–769), respectively. Non-hematologic toxicities were moderate, including generalized weakness/fatigue, nausea/vomiting, diarrhea and anorexia. One patient required dose reduction; three patients required dose delays. NSC 655649 at this dose and schedule is inactive against advanced previously minimally treated metastatic colorectal cancer and further study of this drug as a single agent in this disease using an every three-week schedule is not warranted.     

Current approaches to novel therapeutics in pancreatic cancer

Pancreatic cancer is one of the most refractory neoplasms to medical treatment. Until now there has been only modest improvement in the treatment of this disease. Standards of care for combined-modality treatment of resectable as well as locally advanced, unresectable disease have not been uniformly accepted to date because of an equivocal or conflicting data. The inception of gemcitabine introduced the new era in the management of metastatic pancreatic cancer, however, new therapeutic approaches still need to be defined. The article discusses the current knowledge of the biology of this lethal disease, its impact on treatment options, and explores novel therapeutic modalities that are likely to improve outcomes and survival for patients in the future.     

New bivalent PKC ligands linked by a carbon spacer: enhancement in binding affinity

Protein kinase C (PKC) is known to play an important role in many signal transduction pathways involved in hormone release, mitogenesis, and tumor promotion. In continuation of our efforts to find highly potent activators of PKC for possible use as Alzheimer's disease therapeutics, we designed and synthesized molecules containing two binding moieties (amides of benzolactams or esters of naphthylpyrrolidones) connected by a flexible spacer chain, which could theoretically bind to both the C1a and C1b activator binding domains of the catalytic region or to the C1 domains of two adjacent PKC molecules. The dimers 2a-g of benzolactam showed a 200-fold increase in affinity to PKCalpha and -delta as the spacer length increased from 4 to 20 carbon atoms. Replacement of the oligomethylene chain with an oligoethylene glycol unit (compounds 2h, 2i) showed a 4000- to 7000-fold decrease in affinity to PKCalpha. The dimers of naphthylpyrrolidones 4a-g did not show any marked improvement in binding affinities to PKC in comparison to the monomers synthesized earlier. The dimer of benzolactam 2e did not show much selectivity for PKCalpha, -betaIota, -delta, -epsilon, and -gamma. The high binding affinity of compounds 2d-g to PKCs gives us the impetus to design additional molecules that would retain this enhanced activity and would also show selectivity for the PKC isoforms.     

The BCL2-family of protein ligands as cancer drugs: the next generation of therapeutics

Selective aberrant cell suicide (ie., apoptosis or programmed cell death) is a hallmark of "nonneoplastic" tissue. In cells that have clonally evolved or in common parlance "cancer cells", apoptosis is either itself aberrant or completely inhibited. Strategies to enhance apoptosis under conditions of cancer cellular stress is an evolving and actively investigated area of experimental therapeutics. Bcl2 proteins are key mediators of the process of apoptosis and ligands to these family of proteins have been described using modern combinatorial, computational and evolutionary small molecule screening approaches. Crystallization of several of the Bcl2 family members has provided clarification of the role of these ligands and provided a clearer mechanism of action for the consequences of ligand binding. In several cases, these ligands (e.g., HA14-1, 2-methoxy antimycin A) induce apoptosis even under conditions of Bcl2 overexpression and if developed preclinically will be promising anticancer agents. This rationale becomes even more striking when one observes overexpression of Bcl2 in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer.     

Microcephaly with plate-like cortical calcification

Congenital malformations of the central nervous system have varied presentations depending on the stage of embryological development when the insult occurred. We report a neonate with microcephaly associated with plate-like cortical calcification, probably secondary to an unidentified insult at around 11-12 weeks post-conceptional age causing an arrest of the proliferative phase. The associated vasculopathy probably caused diffuse cortical calcification.     

Characterization of successful and failed autoresuscitation in human infants,including those dying of SIDS

Our purpose was to identify and further characterize physiologic mechanisms relevant to autoresuscitation from hypoxic apnea in infants dying suddenly and unexpectedly. We studied cardiorespiratory recordings of 24 infants (age range, 0.8-21 months) who died suddenly while being monitored at home. These recordings were analyzed for features indicated by studies in animal models to be characteristic of hypoxic gasping, and of recovery from bradycardia and apnea associated with gasping (e.g., autoresuscitation). Findings in 5 infants diagnosed as having sudden infant death syndrome were compared with 6 non-SIDS infants whose deaths resulted from other conditions. Additionally, we studied 15 healthy infants during sleep, using home monitor and other respiratory recording techniques, in order to obtain comparison data. We found in recordings from 23 of 24 subjects that hypoxic gasps with characteristic features occurred immediately preceding death. A unique pattern of complex, closely spaced gasps ("double" or "triple" gasps) was present in many subjects. Evidence of partially successful autoresuscitation closely following one or more gasps occurred in 11 subjects, while another 4 had evidence of complete autoresuscitation with return of normal heart rate and resolution of apnea on one or more occasions. Significant differences between SIDS infants and those dying from other causes included increased occurrence of complex gasps and decreased occurrence of partial or complete autoresuscitation in the SIDS infants. The non-SIDS cases were different from the SIDS cases in that only one had "double" gasps (n = 7), while none had "triple" gasps, as compared with 4 out of 5 SIDS cases with these patterns (P < 0.05, chi-square). Also, in contrast with the SIDS cases, more of the cases with specific postmortem diagnoses had evidence of partial (5 out of 6 cases) or complete (1 out of 6 cases) autoresuscitation (P < 0.05, chi-square). We conclude that partial or complete autoresuscitation by gasping is not uncommon in moribund infants during the first year of life. Failure of autoresuscitation mechanisms other than failure to initiate gasping may be characteristic of infants dying of SIDS. Some SIDS infants appear to be different from infants dying with other diagnoses with respect to efficacy and characteristics of hypoxic gasping.     

Health assessment of U.S. Army Rangers

PURPOSE: Assess the health behaviors of U.S. Army Rangers, including their diet and physical activity patterns, and their use of alcohol, tobacco, and nutritional supplements. METHODS: Army Rangers (N=38) completed selected self-report and food frequency questionnaires, and anthropometric measures (height, weight, circumferences) were taken. RESULTS: Dietary patterns were collected from questionnaires that asked respondents to report the frequency of usual consumption from a list of foods over a period of 1 year. The data collected indicated a diet high in fat (38.0% of energy) and low in carbohydrates (41.9%). Protein intake (17.9% of energy) was consistent with recommendations for endurance and strength training athletes. Hours engaged in physical activity averaged 12 per week. Overall, 76% of the volunteers reported using alcohol on a regular basis, and 52.6% used some form of tobacco: 50% reported using either snuff or chewing tobacco. The use of supplements was high with 13% taking creatine and ephedrine products on a regular basis. CONCLUSION: Although physical activity patterns indicated a high level of activity, dietary and other health behaviors, such as smoking, alcohol use, and patterns of supplement use, suggest that health education programs may be important in this select Army population.