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Saving the Male Breast: A Systematic Literature Review of Breast-Conservation Surgery for Male Breast Cancer
Background: Male breast cancer (MBC) management is extrapolated from female BC. Mastectomy remains the most frequently used surgical procedure for male breast cancer (MBC). We performed a literature review to assess the use of breast-conservation (BCS) in MBC as well as outcomes following BCS. Methods: A systematic literature was performed, and articles screened to identify studies that measured overall survival (OS), disease-free survival (DFS), or local recurrence (LR) in patients undergoing BCS. Weighted averages based on study size were performed for LR, DFS, and 5-year OS. Results: Eight studies met the inclusion criteria with male breast surgery cases, and 859 (14.7%) underwent BCS. The mean follow-up time was 53 months, and mean age was 62.6 years, with stage II as the most common presentation. Two studies reported that 50–71.4% of patients underwent sentinel lymph node biopsy, and four studies reported axillary lymph node dissection in 14.3–100%. Five studies reported on adjuvant radiation therapy in 12.0–100% of total patients undergoing BCS. Four studies reported use of hormonal therapy in 73.8–100% of patients. Four studies reported use of chemotherapy in 25–66.7% of patients. Seven studies reported LR among 116 patients, with a weighted average of 9.9%. Three studies reported on DFS in 14 patients, with a weighted average 85.6%. Two studies report OS in 143 patients with a weighted average of 84.4%. Conclusions: Breast conservation may be considered a safe alternative in the surgical treatment of MBC. Future research should focus on better standardization of local therapy for MBC and improved reporting of outcomes.
Repeated exposure to eucalyptus wood smoke alters pulmonary gene and metabolic profiles in male Long-Evans rats
Abstract Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.
Circulating and skeletal muscle microRNA profiles are more sensitive to sustained aerobic exercise than energy balance in males
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Fundamental investigation of losses of skeletal mineral in young adult human male and collaterallyin young adult male pigtail monkeys /macacus memestrina/ through immobilization for varying periods of time, coupled with a study of methods of preventi
Bed rest study of radiographic bone density and urine analysis for calcium and phosphorus
Fundamental investigation of losses of skeletal mineral in young adult human males and collaterally in young adult male pigtail monkeys /macacus nemestrima/ through immobilization for varying periods of time, coupled with a study of methods of preven
Skeletal mineral losses in young adult humans and monkeys resulting from immobilization
Developmental changes in skin collagen biosynthesis pathway in posthatch male and female chickens
The developmental changes in skin collagen biosynthesis pathway in male and female chickens were evaluated. Concentration of collagen, levels of mRNA for collagen type I subunits and for lysyl hydroxylase, and the level of three lysyl oxidase-derived cross-links: dehydro-dihydroxylysinonorleucine (DHLNL), dehydro-hydroxylysinonorleucine (HLNL), and dehydro-histidinohydroxymerodesmosine (HHMD) were determined during 4 wk posthatching. Skin collagen content increased with age and was higher in males than in females. In both sexes, the expression of the genes coding for alpha 1 and alpha 2 of collagen type I decreased with age: alpha 1(I) gene expression decreased from Day 3 onwards, whereas the reduction in alpha 2(I) gene expression started 1 wk later. At all ages examined, the expression of both genes was higher in male than in female skin. Males and females lysyl hydroxylase gene expression remained low until Day 16, after which an increase in the enzyme gene expression was observed. An increase in skin HLNL content was observed from Day 3 in both sexes reaching a peak in males at Day 9 and in females 1 wk later. The DHLNL content, which was higher in males than in females at all ages tested, dramatically decreased in both male and female skin from 3 d of age, reaching its lowest level at Day 16, and remained at that low level thereafter. The skin content of HHMD in males and females followed an oscillatory behavior with higher peaks in the male skin. The results suggest that the higher tensile strength of male skin than female skin may be due to the elevated skin collagen content that resulted from increased expression in collagen type I genes on the one hand, and from the higher amounts of various collagen cross-links on the other.
Male mating season range expansion results from an increase in scale of daily movements for a polygynous–promiscuous bird
Abstract Males of species with promiscuous mating systems are commonly observed to use larger ranges during the mating season relative to non‐mating seasons, which is often attributed to a change in movements related to reproductive activities. However, few studies link seasonal range sizes to variation in daily space use patterns to provide insight into the behavioral mechanisms underlying mating season range expansion. We studied 20 GPS‐tagged male wild turkeys ( Meleagris gallopavo ), a large upland gamebird, during the mating and summer non‐mating seasons to test the hypothesis that larger mating season ranges resulted from male wild turkeys expanding the scale of daily movement activities to locate and court females. We delineated mating and non‐mating seasons based on intensity of gobbling, a vocalization tied to courtship behavior, recorded by autonomous recording units distributed across the study area. Mating season ranges were significantly larger than non‐mating season ranges. Daily ranges were larger in the mating season, as were distances between roost sites used on consecutive nights. Variance in daily range size was greater in the mating season, but low temporal autocorrelation suggested considerable daily variability in both seasons. We found no evidence that male wild turkeys changed how they distributed daily movements within seasonal ranges, or differences in habitat use, suggesting larger mating season ranges result from male wild turkeys increasing the scale of their daily movements, rather than a systematic shift to a nomadic movement strategy. Likely, the distribution of females is more dynamic and ephemeral compared to other resources, prompting males to traverse larger daily ranges during the mating season to locate and court females. Our work illustrates the utility of using daily movement to understand the behavioral process underlying larger space use patterns.
DIFFERENTIAL CANID PREDATION OF TRANSLOCATED JUVENILE DESERT TORTOISES AND CHEMICAL SIGNATURE DIFFERENCES BETWEEN FEMALE AND MALE ADULT AND JUVENILE DESERT TORTOISES
Differential predation was observed in a population of 59 translocated juvenile Desert Tortoises (Gopherus agassizii) of known sex during a juvenile translocation survival study between September 2012 and November 2017. The main source of mortality (77%; 24 of 31 deaths) was attributed to Coyote (Canis latrans) and Kit Fox (Vulpes macrotis) predation. Predation was skewed with 71% (n = 17) female mortality versus 29% (n = 7) male mortality. We tested the hypothesis that juvenile females smell different than males which leads to increased canid predation. We also explored differences in chemical signatures of resident adult female and male Desert Tortoises. We collected oral, cloacal and chin/forelimb swabs from translocated juvenile and resident adult female and male tortoises during fall 2015 and fall 2017 and analyzed them using headspace gas chromatography/mass spectrometry to determine potential differences in the chemical signatures among the four groups. Standardized chromatographic peak responses were subjected to repeated analyses of variance (ANOVA). For development of artificial scents, mean responses were calculated for each juvenile tortoise from standardized responses representing all collections (i.e., oral, cloacal, and chin/forelimb swabs) and grand means were determined for males and females. Repeated measures ANOVAs clearly demonstrated that the collections of volatiles differed according to age and/or sex depending on the body location of collection. Among the plausibly endogenous volatiles that differed by age, many of them are alcohols. Two field trials using captive Coyotes and one field trial partially within the translocation area were conducted to test if Coyotes showed a preference for female or bias against male synthesized scent. No consistent preference or bias was shown, suggesting that no innate preference for female odor was evident.
Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling
Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. The objective of this study was to determine the thermal and physiologic responses of patients with multiple sclerosis to short-term maximal head and neck cooling. A Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used to cool the head and neck regions of 24 female and 26 male patients with multiple sclerosis in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 degrees C), were cooled for 30 min by the liquid cooling garment, which was operated at its maximum cooling capacity. Oral, right, and left ear temperatures and cooling system parameters were logged manually every 5 min. Forearm, calf, chest, and rectal temperatures, heart rate, and respiration rate were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. This protocol was performed during the winter and summer to investigate the seasonal differences in the way patients with multiple sclerosis respond to head and neck cooling. No significant differences were found between the male and female subject group's mean rectal or oral temperature responses during any phase of the experiment. The mean oral temperature decreased significantly (P < 0.05) for both groups approximately 0.3 degrees C after 30 min of cooling and continued to decrease further (approximately 0.1-0.2 degrees C) for a period of approximately 15 min after removal of the cooling helmet. The mean rectal temperatures decreased significantly (P < 0.05) in both male and female subjects in the winter studies (approximately 0.2-0.3 degrees C) and for the male subjects during the summer test (approximately 0.2 degrees C). However, the rectal temperature of the female subjects did not change significantly during any phase of the summer test. These data indicate that head and neck cooling may, in general, be used to reduce the oral and body temperatures of both male and female patients with multiple sclerosis by the approximate amount needed for symptomatic relief as shown by other researchers. However, thermal response of patients with multiple sclerosis may be affected by gender and seasonal factors, which should be considered in the use of liquid cooling therapy.
Targeted seed EMS mutagenesis reveals a basic helix–loop–helix transcription factor underlying male sterility in sorghum
Abstract Forward genetic screens of mutant populations are fundamental for functional genomics studies. However, isolating independent mutant alleles to molecularly identify causal genes is challenging in species recalcitrant to genetic manipulation. Here, we demonstrate that classic seed ethyl methanesulfonate (EMS) mutagenesis coupled with genome sequencing can overcome this limitation in sorghum. We used this method to generate new mutant alleles of sorghum MALE STERILE 8 (MS8) and identified the causal locus for the ms8 phenotype as Sobic.004G270900, which encodes the sorghum ortholog of maize bhlh122, a basic helix–loop–helix (bHLH) transcription factor required for male fertility in maize. Bulked segregant analysis mapped ms8-1 to a region on chromosome 4 containing Sobic.004G270900. Seeds from heterozygous MS8/ms8-1 plants were mutagenized and screened for chimeric inflorescences containing sectors with white, sterile anthers resembling the ms8-1 homozygous phenotype. DNA sequencing of sterile and fertile sectors from a single chimeric inflorescence revealed two mutations in Sobic.004G270900 within the sterile sector, but not the fertile sector. Isolation of this loss-of-function allele (ms8-2) established Sobic.004G270900 as the causative locus for male sterility in the ms8 mutant. We generated additional alleles of MS8 in a different genetic background using CRISPR/Cas9-based gene editing, where deletions in Sobic.004G270900 also resulted in male sterility. Our work identified a gene underlying male sterility in sorghum and provides a novel and straightforward genetic tool for researchers who lack access to advanced transformation facilities to validate gene candidates. Unlike gene editing, no prior knowledge of candidate genes is required for targeted seed EMS mutagenesis to aid identification of causal loci.
Characterization and Development of the Male Shoulder Shield in an Introduced Wild Pig Population
A sample of 721 males from an introduced wild pig population in western South Carolina was examined to better describe the unique structure known as the shoulder shield in this species. The shield initially developed as early as 9-12 months of age, and then increased to be found in all adults (36 months of age or older). Growth of the structure began in the central lateral shoulder region and increased to cover an area extending from the posterior neck back to the anterior hips, and from the middorsum down to the proximal margin of the exposed portion of the front leg. The shield dimensions (i.e., length, height and thickness) increased with age, physical size, and body mass of the boar. The thickness varied seasonally, being greatest during the annual peak of conception. The thickness was also positively correlated with the animal’s body condition, implying a potential for a nutritional influence affecting that dimension, and possibly also an energy storage function. Injuries indicative of male-male fighting were primarily found on portions of the body covered by the shield. This corroborates the function of this structure as being protective in such male-male aggressive encounters in this species.
Comparison of circadian rhythms in male and female humans
Heart rate (HR) and rectal temperature (RT) data were obtained from 12 female and 27 male subjects. The subjects were housed in a facility where the environment was controlled. Human male and female RT and HR exhibit a circadian rhythm with an excursion of about 1.2 C and 30 beats/min, respectively. The acrophases, amplitudes, and level crossings are only slightly different between the sexes. The male HR and RT circadian wave forms are more stable than those of the females. However, the actual RT and HR of males were always lower than that of females at all time points around the clock. The HR during sleep in females is 15 per cent below the daily mean heart rate and in males, 22 per cent.
The Effect of Hindlimb Suspension on the Reproductive System of Young Male Rats
Colonization of space requires the ability to reproduce in reduced gravity. Following spaceflight, astronauts and male rats exhibit decreased testosterone (T). This has important implications as T effects the testes and accessory sex glands. To our knowledge no studies have examined the effects of spaceflight on accessory sex glands. Due to the rarity of spaceflight opportunities, ground models have been used to simulate weightlessness. The objective of this study was to determine the effect of long-term (21 d) weightlessness on the reproductive system of male rats. Weightlessness was simulated using the Morey-Holton hindlimb suspension (HLS) model. Age 10 week old, male Sprague-Dawley rats weighing (209.0 +9.7g) were randomly assigned (n=10/group) to either HLS or ambulatory control. In HLS rats, testes mass was 33% lower (p<0.05) than ambulatory controls. However, HLS had no effect on prostate (0.65 +0.09g vs 0.69 +0.12g) or seminal vesicles (1.01 +0.35g vs 0.75 +0.22g) weights compared to controls. The absence of effects on plasma T in this study contrasts previous reports of reduced plasma T in HLS male rats. This discrepancy may have been due to the age of animal and timing of sampling. T levels vary dramatically during testes development as well as within normal diurnal cycles. In young HLS rats, testes weight was reduced but not plasma T. Subsequently there was no effect on accessory sex glands. However, this may not be the case in older rats. More studies using standardized methods are needed to gain a better understanding of male reproduction function and capability in weightlessness. Funding provided by NASA.
Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects
Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.
Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation
As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.
Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation
As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.