Evaluation of a digital FFQ using 24 h recalls as reference method, for assessment of habitual diet in women with South Asian origin in Norway.

OBJECTIVE: Dietary assessment tools should be designed for the target population. We developed an FFQ designed to assess diet in South Asian women in Norway. The study objective was to evaluate this FFQ using 24-h dietary recalls as reference method. DESIGN: Approximately 3 weeks after the participants (n 40) had filled in the FFQ, the first of three non-consecutive 24-h dietary recalls was completed. The recalls were telephone-based, unannounced and performed by a trained dietitian, with 2-3 weeks between each interview. SETTING: The DIASA 1 study, in Oslo, Norway. PARTICIPANTS: Women of South Asian ethnic origin participating in the DIASA 1 study were invited to participate in the evaluation study. RESULTS: The WebFFQasia significantly overestimated the absolute intake of energy, protein, fat and carbohydrates compared with the 24-h dietary recalls. Absolute intakes of sugar, starch and fibre did not differ significantly between the methods. For energy percentages (E%), there were no significant differences, except for monounsaturated fat. Correlations were strong for E% from sugar and saturated fat and moderate for E% from fibre, carbohydrate, total fat and protein. Fourteen food groups out of twenty three were not significantly different compared with the reference method, and sixteen groups showed strong to moderate correlations. CONCLUSION: The WebFFQasia may be used to assess E% from habitual diet and can adequately estimate intakes and rank participants according to nutrient intake and main food categories at group level.

Empowered, Yet Vulnerable: Motives for Sport Participation, Health Correlates, and Experience of Sexual Harassment in Female Combat-Sport Athletes.

Background: To explore motives for combat sport participation, weight regulation practices, symptoms of low energy availability (LEA), disordered eating (DE) or eating disorders (ED), and any experiences with sexual harassment (SH) among female combat-sport athletes. Methods: In total, 29 athletes were recruited by social media and in clubs. Participants responded to a questionnaire on health behavior and mental health and completed diet registration and a DXA-scan. Results: Most athletes started combat sports to feel empowered and experienced an inclusive milieu, but the frequency of health issues was high. A total of 21−67% had symptoms of ED, suffered from injuries, had low site-specific BMD, and/or symptoms of LEA. Athletes had insufficient intake of energy and nutrients, and <50% received any dietary information or guidance from their clubs. Most athletes complied with favorable weight-loss strategies; still, >20% used unfavorable methods and rapid weight-loss periods. A total of 70% of the athletes had experienced SH, of which 41% experienced SH within the combat-sport context. Conclusion: Combat sport offers an inclusive milieu, which may increase women's health and confidence; still, our results indicates a need for actions to safeguard female combat-sport athletes' mental and physical health, implying a cultural change within the community of combat sport and a need for increased health and nutrition literacy.

Synthesis and Anticancer Evaluation of Sulfur Containing 9-anilinoacridines.

BACKGROUND: DNA topoisomerases are a class of enzymes that play a critical role in fundamental biological processes of replication, transcription, recombination, repair and chromatin remodeling. Amsacrine (m-AMSA), the best-known compound of 9-anilinoacridines series, was one of the first DNA-intercalating agents to be considered a Topoisomerase II inhibitor. OBJECTIVES: A series of sulfur-containing 9-anilinoacridines related to amsacrine were synthesized and evaluated for their anticancer activity. METHODS: Cell viability was assessed by the MTT assay. The topoisomerase II inhibitory assay was performed using the Human topoisomerase II Assay kit, and flow cytometry was used to evaluate the effects on the cell cycle of K562 cells. Molecular docking was performed using the Schrödinger Maestro program. RESULTS: Compound 36 was found to be the most cytotoxic of the sulfide series against SW620, K562, and MCF-7. The limited SAR suggested the importance of the methansulfonamidoacetamide side chain functionality, the lipophilicity, and the relative metabolic stability of 36 in contributing to the cytotoxicity. Topoisomerase II α inhibitory activity appeared to be involved in the cytotoxicity of 36 through the inhibition of decatenation of kinetoplast DNA (kDNA) in a concentration- dependent manner. Cell cycle analysis further showed Topo II inhibition through the accumulation of K562 cells in the G2/M phase of the cell cycle. The docking of 36 into the Topo II α-DNA complex suggested that it may be an allosteric inhibitor of Topo II α. CONCLUSION: Compound 36 exhibits anticancer activity by inhibiting topoisomerase II, and it could further be evaluated in in vivo models.

Structural and biological aspects of natural bridged macrobicyclic peptides from marine resources.

Among peptide-based drugs, naturally occurring bicyclic compounds have been established as molecules with unique therapeutic potential. The diverse pharmacological activities associated with bicyclic peptides from marine tunicates, sponges, and bacteria render them suitable to be employed as effective surrogate between complex and small therapeutic moieties. Bicyclic peptides possess greater conformational rigidity and higher metabolic stability as compared with linear and monocyclic peptides. The antibody-like affinity and specificity of bicyclic peptides enable their binding to the challenging drug targets. Bridged macrobicyclic peptides from natural marine resources represent an underexplored class of molecules that provides promising platforms for drug development owing to their biocompatibility, similarity, and chemical diversity to proteins. The present review explores major marine-derived bicyclic peptides including disulfide-bridged, histidinotyrosine-bridged, or histidinoalanine-bridged macrobicyclic peptides along with their structural characteristics, synthesis, structure-activity relationship, and bioproperties.The comparison of these macrobicyclic congeners with linear/monocyclic peptides along with their therapeutic potential are also briefly discussed.

Early prognostication of COVID-19 to guide hospitalisation versus outpatient monitoring using a point-of-test risk prediction score.

INTRODUCTION: Risk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking. METHODS: Multivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290). RESULTS: 983 patients (median age 70, IQR 53-83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0-1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%). CONCLUSION: The SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.

Adoption of Gla-100 in India and its Impact on Insulin Usage Patterns.

Fueled by perceptions regarding Indian dietary patterns and premixed insulin's claim to fame of providing dual fasting and post-prandial control, there was a greater inclination towards using premixed insulins in clinical practice until the last decade. However, the advent of insulin glargine 100 U/mL (Gla-100) opened up a new dimension in insulin therapy landscape in India. The data from the last 5 years reveal that Gla-100 has gained more traction among Indian clinical practitioners. Basis evidences that have emerged from various clinical studies, this present review elaborates on certain key issues which have helped Gla-100 carve its own niche and effected a progressive shift in insulin prescription pattern in India.

Higher than reported adolescent and young adult clinical trial enrollment during the "Golden Age" of melanoma clinical trials.

Clinical trial enrollments in adolescents and young adults (AYA) with cancer have historically been lower than those in pediatric and older adult populations. We sought to examine therapeutic trial enrollment rates at our cancer center. We performed a retrospective evaluation of AYA patients treated before and after the first checkpoint inhibitor trial opened at our cancer center in 2007. We examined gender, stage at presentation and insurance status in terms of trial enrollment. We compared the trial participation rate of AYA patients with that of older adults. In this adult facility, 12.7% (1,831) of total patients were between age 15 and 39. Overall therapeutic clinical trial rate was 17.6% which increased to 19.8% since 2007. Both nodal disease or metastatic disease at presentation was associated with increasing odds of trial enrollment (OR = 5.36 and P < 0.001 for nodal disease and OR = 7.96 and P < 0.001 for metastatic disease). There was a nonstatistically significant trend toward improved 3-year overall survival in the AYA patients with advanced presentation that enrolled on clinical trials compared with those not enrolled on trials since 2007. AYA clinical trial enrollment at a comprehensive care center melanoma program was higher than reported in the literature overall for AYA patients. This 1,831 patient cohort may provide a foundation for more detailed investigation toward quantifying the effects of clinical trial enrollment in terms of age-specific benefits and toxicities for AYA patients with malignancies that have their peak incidence in older adults.

Pediatric Melanoma and Atypical Melanocytic Neoplasms.

Melanoma is uncommon in the pediatric age range, but is increasing in frequency and often presents with atypical features compared to the classic ABCDE criteria common to adult melanoma cases. Moreover, many melanocytic neoplasms in childhood pose diagnostic challenges to the pathologist, and sometimes cannot be unequivocally classified as benign nevi or melanoma. This chapter addresses the evaluation and management of pediatric patients with melanoma and atypical melanocytic neoplasms, including the roles of and unresolved questions surrounding sentinel lymph node biopsy, completion lymphadenectomy, adjuvant therapy, and treatment of advanced disease.

Efficacy of hyaluronic acid (hyaluronan) in root coverage procedures as an adjunct to coronally advanced flap in Millers Class I recession: A clinical study.

BACKGROUND: The purpose of this study was to assess the efficacy of hyaluronic acid (HA) in root coverage procedures as an adjunct to coronally advanced flap (CAF) procedure. MATERIALS AND METHODS: This was a randomized clinical trial with split mouth design, where 10 patients with 20 sites of Millers Class I recession were treated and followed-up for a period of 6 months. CAF procedure was performed, HA was applied onto the experimental sites before suturing the flap. Recession depth (RD) was measured regularly at baseline 1, 3, 6, 12, and 24 weeks postoperatively. Probing pocket depth (PPD) and clinical attachment level (CAL) were also measured along with RD at baseline and 12 and 24 weeks. RESULTS: There was a significant change in RD, PPD, CAL, and percentage of root coverage in both groups when compared to the baseline values. There was no statistically significant difference between experimental and control group in terms of RD (P = 0.917), PPD (P = 0.917) and CAL (P = 0.761). RD was 3.2 mm ± 0.78 mm in experimental site and control sites 2.9 mm ± 0.73 mm reduced to 1.1 mm ± 0.99 mm in experimental sites and 1.0 mm ± 0.66 mm in control sites. Though, there is no statistically significant difference root coverage in the experimental group appeared to be clinically more stable compared with the control group after 24 weeks. CONCLUSIONS: This study suggests that use of HA may improve the clinical outcome of root coverage with CAF procedure.

Oral acetazolamide after Boston keratoprosthesis in Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare but severe and sometimes fatal condition associated with exposure to medications; sulfamethoxazole is among the most common causes. We sought to address the safety of acetazolamide, a chemically related compound, in patients with prior SJS/TEN and glaucoma. A retrospective case series is described of patients at the Massachusetts Eye and Ear Infirmary who underwent keratoprosthesis surgery for corneal blindness from SJS/TEN, and later required oral acetazolamide for elevated intraocular pressure. FINDINGS: Over the last 10 years, 17 patients with SJS/TEN received a Boston keratoprosthesis. Of these, 11 developed elevated intraocular pressure that required administration of oral acetazolamide. One of 11 developed a mild allergic reaction, but no patient experienced a recurrence of SJS/TEN or any severe adverse reaction. CONCLUSION: Although an increase in the rate of recurrent SJS/TEN due to oral acetazolamide would not necessarily be apparent after treating only 11 patients, in our series, acetazolamide administration was well tolerated without serious sequela.

Current state of in vivo confocal microscopy in management of microbial keratitis.

PURPOSE: The purpose of this study was to review the current literature on in vivo confocal microscopy of the cornea and to discuss the current clinical indications for its use in microbial keratitis. METHODS: Review of select recent literature on in vivo confocal microscopy and atypical microbial keratitis. RESULTS: Delayed diagnosis of Acanthamoeba and fungal keratitis is typical, resulting in significant vision loss. This is partially due to the low sensitivity and time delay of corneal cultures. In the hands of an experienced viewer, the confocal microscope has been found to have a sensitivity of up to 90% in the diagnosis of Acanthamoeba keratitis and close to 80% for fungal keratitis. CONCLUSION: In vivo confocal microscopy is emerging as a tool for rapid diagnoses in severe infectious keratitis with high sensitivity. In addition, it can be used to monitor treatment response, allowing guidance to clinicians for medical or surgical management.

Corneal sensation after descemet stripping and automated endothelial keratoplasty.

PURPOSE: To measure corneal sensation after Descemet stripping and automated endothelial keratoplasty (DSAEK). METHODS: Prospective comparative case series involving 52 eyes of 29 patients in the early postoperative period (<6 months) after small-incision DSAEK. Patients' contralateral eye served as a control. The sample size calculation was calculated assuming an alpha error of 0.05 and a beta error of 0.2. This determined that a sample size of 11 patients would be sufficient to detect a difference in corneal sensation of 5 mm as measured with the Cochet-Bonnet esthesiometer. The nylon filament was used to measure threshold sensation at 9 points on the operative eye and 5 points on the control. The data were analyzed using the paired samples test. RESULTS: Although the results demonstrated mild hypesthesia of the corneal epithelium overlying the donor lenticule, we found no statistically significant difference in corneal sensation at the central point when comparing the DSAEK cornea with the control (57 vs 59 mm, P = 0.13.) In addition, when comparing corresponding points on the epithelium overlying the DSAEK graft and host cornea, no significant difference was found (57 vs 58 mm, P = 0.32). A difference was detected when comparing the average corneal sensation of the DSAEK eye with the control, but careful analysis of the data shows that this was driven by the slight decrease in sensitivity at the temporal incisional point (57 vs 59 mm, P = 0.002). CONCLUSIONS: The results of this prospective study demonstrate the relative preservation of corneal sensitivity after DSAEK. Preservation of corneal sensation may provide another advantage of DSAEK over traditional penetrating keratoplasty.

External refinement of the donor lenticule position during descemet's stripping and automated endothelial keratoplasty.

The authors describe a technique to facilitate the centration of the donor lenticule during Descemet's stripping and automated endothelial keratoplasty. The donor corneal lenticule is unfolded and grossly centered in the anterior chamber using a barbed 30-gauge needle on a 3-cc air syringe or a reverse Sinsky hook. Fine adjustments to center the lenticule can be achieved by applying external pressure to the cornea with a laser in-situ keratomileusis flap roller. This simple technique provides a mechanism for simultaneously removing interface fluid and allows the surgeon to center the donor corneal lenticule without further risk of direct mechanical trauma to the donor endothelium.

Enhancement of chaperone function of alpha-crystallin by methylglyoxal modification.

The molecular chaperone function of alpha-crystallin in the lens prevents the aggregation and insolubilization of lens proteins that occur during the process of aging. We found that chemical modification of alpha-crystallin by a physiological alpha-dicarbonyl compound, methylglyoxal (MG), enhances its chaperone function. Protein-modifying sugars and ascorbate have no such effect and actually reduce chaperone function. Chaperone assay after immunoprecipitation or with immunoaffinity-purified argpyrimidine-alpha-crystallin indicates that 50-60% of the increased chaperone function is due to argpyrimidine-modified protein. Incubation of alpha-crystallin with DL-glyceraldehyde and arginine-modifying agents also enhances chaperone function, and we believe that the increased chaperone activity depends on the extent of arginine modification. Far- and near-UV circular dichroism spectra indicate modest changes in secondary and tertiary structure of MG-modified alpha-crystallin. LC MS/MS analysis of MG-modified alpha-crystallin following chymotryptic digestion revealed that R21, R49, and R103 in alphaA-crystallin were converted to argpyrimidine. 1,1'-Bis(4-anilino)naphthalene-5,5'-disulfonic acid binding, an indicator of hydrophobicity of proteins, increased in alpha-crystallin modified by low concentrations of MG (2-100 microM). MG similarly enhances chaperone function of another small heat shock protein, Hsp27. Our results show that posttranslational modification by a metabolic product can enhance the chaperone function of alpha-crystallin and Hsp27 and suggest that such modification may be a protective mechanism against environmental and metabolic stresses. Augmentation of the chaperone function of alpha-crystallin might have evolved to protect the lens from deleterious protein modifications associated with aging.