Optical spectroscopic determination of human meniscus composition

This study investigates the correlation between the composition of human meniscus and its absorption spectrum in the visible (VIS) and near infrared (NIR) spectral range. Meniscus samples (n = 24) were obtained from nonarthritic knees of human cadavers with no history of joint diseases. Specimens (n = 72) were obtained from three distinct sections of the meniscus, namely; anterior, center, posterior. Absorption spectra were acquired from each specimen in the VIS and NIR spectral range (400–1,100 nm). Following spectroscopic probing, the specimens were subjected to biochemical analyses to determine the matrix composition, that is water, hydroxyproline, and uronic acid contents. Multivariate analytical techniques, including principal component analysis (PCA) and partial least squares (PLS) regression, were then used to investigate the correlation between the matrix composition and it spectral response. Our results indicate that the optical absorption of meniscus matrix is related to its composition, and this relationship is optimal in the NIR spectral range (750–1,100 nm). High correlations (R²_uronic = 86.9%, R²_water = 83.8%, R²_{hydroxyproline} = 81.7%, p < 0.0001) were obtained between the spectral predicted and measured meniscus composition, thus suggesting that spectral data in the NIR range can be utilized for estimating the matrix composition of human meniscus. In conclusion, optical spectroscopy, particularly in the NIR spectral range, is a potential method for evaluating the composition of human meniscus. This presents a promising technique for rapid and nondestructive evaluation of meniscus integrity in real‐time during arthroscopic surgery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:270–278, 2016.     

Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies

Purpose

The purpose of this study is to investigate if female patients with lymphoma demonstrate diminished ovarian reserve prior to initiation of the lymphoma treatment.

Methods

Sixty-four patients with newly diagnosed lymphoma undergoing controlled ovarian hyperstimulation for fertility preservation were compared with 365 healthy controls undergoing elective oocyte cryopreservation (controlled ovarian hyperstimulation (COH)) and 128 patients with other types of malignancy prompting fertility preservation. The data of all lymphoma patients, all elective, and all the patients with other types of malignancy who met the inclusion criteria and underwent COH for fertility preservation during the study period were retrospectively analyzed. Primary outcomes included serum anti-Müllerian hormone (AMH) levels (ng/mL) and antral follicle count (AFC).

Results

Patients in the lymphoma group demonstrated significantly lower AMH levels and AFC and had less oocytes harvested and cryopreserved when compared to healthy controls as well as patients with other malignancies.

Conclusion

Patients with lymphoma demonstrate diminished ovarian reserve when compared with healthy controls and patients with other malignancies. This should be taken into consideration when deciding on the dose for COH.

     

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor–related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor–related TMA. ADAMTS13^−/− mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor–related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13^−/− mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.     

Pyrimethamine-resistant dihydrofolate reductase enzymes of Plasmodium falciparum are not enzymatically compromised in vitro

Plasmodium falciparum, the protozoan that causes the most lethal form of human malaria, has been controlled principally by two safe, affordable drugs, chloroquine and sulfadoxine-pyrimethamine (SP). Studies in the laboratory and in the field have demonstrated that resistance to SP depends on non-synonymous point mutations in the dihydrofolate reductase (DHFR), and dihydropteroate synthase (DHPS) coding regions. Parasites that carry dhfr genes with 3 or 4 point mutations (51I/59R/108N triple mutation or 51I/59R/108N/164L quadruple mutation) are resistant to pyrimethamine in vitro and patients infected with these parasites respond poorly to SP treatment. The wide spread of these pyrimethamine-resistant alleles demonstrates the increased fitness over drug-sensitive alleles in the presence of the drug. However, it is not clear whether these alleles might reduce the fitness of parasites in the absence of drug pressure. As a first step, we compared the kinetic properties of the wild type, and three mutant alleles to determine whether the native DHFR-thymidylate synthase form of the mutant proteins showed compromised activity in vitro. The mutant enzymes had K(m) values for their substrate, dihydrofolate that were significantly lower than the wild type, k(cat) values in the same range as the wild type enzyme, and k(cat)/K(m) values higher than wild type. In contrast, the K(m) values for the NADPH cofactor were higher than wild type for the mutant enzymes. These observations suggest that the fitness of these parasites may not be compromised relative to those that carry the wild type allele, even without sustained SP drug pressure.     

Carimune NF Liquid is a Safe and Effective Immunoglobulin Replacement Therapy in Patients with Primary Immunodeficiency Diseases

Subjects with primary immune deficiency diseases treated with intravenous immunoglobulin (n=42) received intravenous infusions of Carimune NF Liquid every 3–4 weeks for 6 months without routine premedication. The mean dose/patient/infusion was 278.5–800.7 mg/kg. Also, 80.4% of infusions achieved maximum rates of ≥3.5 mg/kg/min; 32% of infusions were associated with adverse events during or within 48 h of their end (upper 95% confidence interval was 39.4%, meeting the Food and Drug Administration (FDA) criterion for acceptable tolerability), and 54.8% of subjects had at least one temporally associated adverse event considered at least possibly drug-related (headache: 35.7% of subjects, 12.4% of infusions; nausea: 14.3%, 3.5%; myalgia: 14.3%, 3.2%; fatigue: 11.9%, 5.7%). The frequencies of these were highest after the first infusion. There were no serious drug-related adverse events or acute serious bacterial infections. Serum IgG trough levels were unchanged from baseline. Carimune NF Liquid, a ready-to-use, high-concentration, liquid immunoglobulin preparation is safe and effective. On behalf of the study group     

Increased Efficacy and Safety of Enteral Nutrition Support with a Protocol (ASNET) in Noncritical Patients: A Randomized Controlled Trial

Background

Unintentional underfeeding is common in patients receiving enteral nutrition (EN), and is associated with increased risk of malnutrition complications. Protocols for EN in critically ill patients have been shown to enhance adequacy, resulting in better clinical outcomes; however, outside of intensive care unit (ICU) settings, the influence of a protocol for EN is unknown.

Descriptive and Prospective Analysis of Young Adult Alcohol Use and Romantic Relationships: Disentangling between- and within-Person Associations Using Monthly Assessments

Background: Prior research on romantic relationships and alcohol use among young adults has not distinguished between differences in patterns of relationship status over extended periods of time and within-person changes in status that only occur for some individuals. Objectives: This study captured between-person differences in relationship patterns, assessed associations between relationship patterns and alcohol use, and examined within-person associations between alcohol use and relationship status changes. In addition, age and sex differences in between- and within-person associations were tested. Methods: We used multilevel modeling of monthly data collected over one year on alcohol use and romantic relationship status from a Seattle area community sample of 620 young adults (ages 18–24). Results: Participants were coded into six relationship pattern groups: (1) single-not-dating (16%), (2) stable-in-a-relationship (30%), (3) single-dating (10%), (4) ended-a-relationship (14%), (5) started-a-relationship (13%), and (6) ended-and-started-a-relationship (18%). Single-not-dating and stable-in-a-relationship groups reported the least drinking across the entire year; the single-dating, ended-a-relationship, and ended-and-started-a-relationship groups reported higher levels of drinking. Examining within-person changes in groups 3–6 revealed increases in drinking associated with months of dating among the single-dating group, months postbreakup among the ended-a-relationship group, and months of breaking up and starting a new relationship among the ended-and-started-a-relationship group. Few differences by age or sex were found for between- or within-person associations. Conclusions: The findings point to heterogeneity in patterns of relationship status over time, differences in relationship patterns associated with variations in drinking, and particular time points of elevated risk for young adults who experience changes in status.     

A qualitative study of cervical cancer and cervical cancer screening awareness among nurses in Ghana

Despite the availability of cervical cancer screening tools, including those that are appropriate for low resource settings, the rates of preventive cervical cancer screening remain extremely low among women in LMICS. Nurse-led education interventions have been proven to be effective at increasing participation in healthcare recommendations. However, there is a need to determine nurses' knowledge of cervical cancer and cervical cancer prevention in order to develop effective health education interventions. Our goal was to assess Ghanaian nurses' knowledge of cervical cancer and cervical cancer prevention. Interviews and small focus groups were conducted with 42 nurses at two hospitals in Ghana. Awareness of cervical cancer was very high among the nurses. However, the majority of the participants held negative perceptions about cervical cancer and lacked knowledge about cervical cancer risk factors and prevention. The results can be used to inform the development of culturally-relevant cervical cancer education interventions targeted towards women and healthcare providers in LMICs.