Chemotherapy-induced ovarian failure: manifestations and management.

Thanks to improvements in treatment regimens, more and more patients are now surviving cancer. However, cancer survivors are faced with the serious long-term effects of the different modalities of cancer treatments. One of these adverse effects is chemotherapy-induced irreversible damage to the ovarian tissues, which leads to premature ovarian failure and its resulting consequences such as hot flashes, osteoporosis, sexual dysfunction and the risk of infertility. Chemotherapy-induced ovarian failure (or chemotherapy-induced premature menopause) affects the quality of life of female cancer survivors. Although there is no clear definition of chemotherapy-induced ovarian failure, irreversible amenorrhoea lasting for several months (>12 months) following chemotherapy and a follicle stimulating hormone level of > or = 30 MIU/mL in the presence of a negative pregnancy test seems to be an appropriate characterisation. Different chemotherapy agents, alkylating cytotoxics in particular, have the potential to cause progressive and irreversible damage to the ovaries. The result of this damage is a state of premature ovarian failure, with progressive declining of estrogen levels, decreasing bone mass and an increased risk of fractures. Historically, hormonal replacement therapy (HRT) has been used to treat menopausal problems in the general population, but concerns about the potential of estrogen to increase the risk of breast cancer in women at high-risk or increase the risk of recurrence in cancer survivors, have forced physicians to utilise alternative treatments. This review discusses some of the newer therapies that are now available to provide appropriate symptom control, avoid complications such as fractures and possibly prevent infertility by making the ovarian epithelium less susceptible to cytotoxic agents.     

Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review.

We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely.     

Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.

PURPOSE: Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). RESULTS: Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. CONCLUSION: These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.     

Geotechnical and Shear Behavior of Novel Lunar Regolith Simulants TUBS-M,TUBS-T,and TUBS-I

The return to the Moon is an important short-term goal of NASA and other international space agencies. To minimize mission risks, technologies, such as rovers or regolith processing systems, must be developed and tested on Earth using lunar regolith simulants that closely resemble the properties of real lunar soil. So far, no singular lunar simulant can cover the multitude of use cases that lunar regolith involves, and most available materials are poorly characterized. To overcome this major gap, a unique modular system for flexible adaptable novel lunar regolith simulants was developed and chemically characterized in earlier works. To supplement this, the present study provides comprehensive investigations regarding geotechnical properties of the three base regolith simulant systems: TUBS-M, TUBS-T, and TUBS-I. To evaluate the engineering and flow properties of these heterogeneous materials under various conditions, shear tests, particle size analyses, scanning electron microscope observations, and density investigations were conducted. It was shown that small grains <25 µm (lunar dust) are highly compressive and cohesive even at low external stress. They are particularly important as a large amount of fine dust is present in lunar regolith and simulants (x₅₀ = 76.7 to 96.0 µm). Further, ring shear and densification tests revealed correlations with damage mechanisms caused by local stress peaks for grains in the mm range. In addition, an explanation for the occurrence of considerable differences in the literature-based data for particle sizes was established by comparing various measurement procedures. The present study shows detailed geotechnical investigations of novel lunar regolith simulants, which can be used for the development of equipment for future lunar exploration missions and in situ resource utilization under realistic conditions. The results also provide evidence about possible correlations and causes of known soil-induced mission risks that so far have mostly been described phenomenologically.     

Association of the Transmembrane Serine Protease-2 (TMPRSS2) Polymorphisms with COVID-19

SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 individuals negative for the SARS-CoV-2 infection confirmed by RT-PCR test and without antibodies anti-SARS-CoV-2. Four TMPRSS2 polymorphisms (rs12329760, rs2298659, rs456298, and rs462574) were determined using the 5′exonuclease TaqMan assays. Under different inheritance models, the rs2298659 (p_codominant2 = 0.018, p_recessive = 0.006, p_additive = 0.019), rs456298 (p_codominant1 = 0.014, p_codominant2 = 0.004; p_dominant = 0.009, p_recessive = 0.004, p_additive = 0.0009), and rs462574 (p_codominant1 = 0.017, p_codominant2 = 0.004, p_dominant = 0.041, p_recessive = 0.002, p_additive = 0.003) polymorphisms were associated with high risk of developing COVID-19. Two risks (ATGC and GAAC) and two protectives (GAGC and GAGT) haplotypes were detected. High levels of lactic acid dehydrogenase (LDH) were observed in patients with the rs462574AA and rs456298TT genotypes (p = 0.005 and p = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574AA genotype (p = 0.028). Our data suggest that the rs2298659, rs456298, and rs462574 polymorphisms independently and as haplotypes are associated with the risk of COVID-19. The rs456298 and rs462574 genotypes are related to high levels of LDH and heart rate.     

Performing under Pressure: Insights into the Diagnostic Testing Burden at a UK National Health Service Clinical Virology Laboratory during the SARS-CoV-2 Pandemic

UK National Health Service (NHS) Clinical Virology Departments provide a repertoire of tests on clinical samples to detect the presence of viral genomic material or host immune responses to viral infection. In December 2019, a novel coronavirus (SARS-CoV-2) emerged which quickly developed into a global pandemic; NHS laboratories responded rapidly to upscale their testing capabilities. To date, there is little information on the impact of increased SARS-CoV-2 screening on non-SARS-CoV-2 testing within NHS laboratories. This report details the virology test requests received by the Leicester-based NHS Virology laboratory from January 2018 to May 2022. Data show that in spite of a dramatic increase in screening, along with multiple logistic and staffing issues, the Leicester Virology Department was mostly able to maintain the same level of service for non-respiratory virus testing while meeting the new increase in SARS-CoV-2 testing.     

Beetroot Juice Produces Changes in Heart Rate Variability and Reduces Internal Load during Resistance Training in Men: A Randomized Double-Blind Crossover

Beetroot juice (BJ) has been used as a sport supplement, improving performance in resistance training (RT). However, its effect on the modulation of the autonomic nervous system has not yet been widely studied. Therefore, the objective of this randomized double-blind crossover study was to assess the effect of acute BJ supplementation compared to placebo in blood pressure (BP), heart rate (HR), heart rate variability (HRV) and internal load during RT measure as Root Mean Square of the Successive Differences between adjacent RR intervals Slope (RMSSD and RMSSD-Slope, respectively). Eleven men performed an incremental RT test (three sets at 60%, 70% and 80% of their repetition maximum) composed by back squat and bench press with. HR, HRV and RMSSD-Slope were measured during and post exercise. As the main results, RMSSD during exercise decrease in the BJ group compared to placebo (p = 0.023; ES = 0.999), there were no differences in RMSSD post-exercise, and there were differences in RMSSD-Slope between groups in favor of the BJ group (p = 0.025; ES = 1.104) with a lower internal load. In conclusion, BJ supplementation seems to be a valuable tool for the reduction in the internal load of exercise during RT measured as RMSSD-Slope while enhancing performance.