In this paper, a novel cataluminescence (CTL)-based sensor array consisting of nine types of catalytic materials is developed for the recognition of several harmful gases, namely carbon monoxide, acetone, chloroform and toluene. First, the experimental setup is constructed by using sensing nanomaterials, a heating plate, a pneumatic pump, a gas flow meter, a digital temperature device, a camera and a BPCL Ultra Weak Chemiluminescence Analyzer. Then, unique CTL patterns for the four types of harmful gas are obtained from the sensor array. The harmful gases are successful recognized by the PCA method. The optimal conditions are also investigated. Finally, experimental results show high sensitivity, long-term stability and good linearity of the sensor array, which combined with simplicity, make our system a promising application in this field. For example, carbon monoxide is widely used in industry, but due to its odorlessness, anesthetic effect and flammability, carbon monoxide can lead to death if people are exposed to it for even a brief time . It may Gas sensors have been widely used in gas control, public safety and environmental protection –7. In reRecently, CTL sensor arrays have attracted great research interest. The major advantage of a CTL sensor array is the ability to collect many kinds of information quickly, such as luminescence intensity, luminescence lifetime, wavelength and spectral shape . FurtherTypically, a CTL sensor image can be used for the detection of a harmful gas, but in many application areas, in order to perfectly and accurately reflect the results, often requires the simultaneous measurement of multiple gases. Researchers have shown increasing interest in developing universal gas sensing systems, such as arrays or column gas sensors. These sensor systems is often named “electronic noses”. An electronic nose usually consists of a cross-sensitivity sensor array and related data processing modules. With an appropriate pattern recognition algorithm, the sensor system has ability to smell and identify several harmful gases in a complex environment. This method is mainly used to solve multiple odor detection problems. As an electronic nose array sensor is composed of different sensing materials, the number of configurations is also different. In 1995, Nakagawa realized this method, as since the catalytic luminescence process is a heterogeneous catalyst reaction, a variety of interactions exist between units at the same time , then a 2O3-based sensors) and improving the image processing technology (by using a data fusion method for the visible and IR image).In our study, we tried to use nine types of catalytic luminescent materials to simultaneously detect harmful gases including carbon monoxide, acetone, chloroform and toluene. These four kinds of harmful gas were detected and discriminated based on their distinct CTL patterns. The CTL patterns were obtained by the sensor array and an imaging method for these harmful gases. Moreover, fast evaluations of carbon monoxide, acetone, chloroform and toluene were carried out at an optimal working temperature. The principle component analysis (PCA) method was used in order to illustrate the selectivity of this sensor array. The analytical characteristics and temperature effect of the CTL-based array were investigated. As a result, the excellent linearity and stability indicated the feasibility of using this array for the determination of carbon monoxide, acetone, chloroform and toluene. The experimental data verified the sensitivity of our sensor imaging method. Finally, our paper conceived the possibility to identify more harmful gases by increasing the types of sensing material used , decorated nanoparticles  and carbonates (BaCO3) were synthesized. The synthesis procedures of these nanomaterials had been investigated and described in previously published papers, such as [A diagram of the sensor device is presented in  such as ,21,23–26In our experiments, a precise flow meter was employed for measurement of the gas flow rate. The temperature of the heating plate was controlled by a digital temperature device. The final CTL patterns were recorded by a camera near the heating plate. All chemicals, including carbon monoxide (purity ≥99.0%), acetone (purity ≥99.5%), chloroform (purity ≥99.7%) and toluene (purity ≥99.5%) used in the experiments had high purity analytical grade. Thus they could be used in our experiments without any further purification. The reagents used in our experiments were purchased from the Shanghai Chemical Reagents Company . The apparatus used for detecting and processing the weak chemiluminescence (CL) signals was a BPCL Ultra Weak Chemiluminescence Analyzer, which was produced by the Biophysics Institute of the Chinese Academy of Sciences . The gas entered the reactor with a flow rate of 200 mL/min. A schematic diagram of the CTL sensor array system is shown in 2.2.A typical image processing application system includes a light source, image capturing system, digital image processing module, intelligent decision-making module and a mechanical control execution module. A camera or another image capturing device converts optical signals into digital signals, then these will be sent to a dedicated image processing system. According to the distribution of pixels, brightness and color information, a series of algorithms will be executed to extract the features. In this section, we talk about the image acquisition, image fusion and pattern recognition of our system.2.2.1.Image acquisition is actually a photoelectric conversion process. It is responsible for capturing the real image of the object, the analog image signal is converted to digital signal, and ultimately into computer data. It provides on-site real-time data for further processing, and directly affects the image quality and image processing effect. Our study focused on the CTL-based imaging method for harmful gases, and aside from exploiting BPCL, we also designed other image acquisition devices according to the characteristics of different applications. There are many advantages of using CTL-based imaging methods for the detection and recognition of harmful gases. The major advantage is the ability to collect CTL emissions from various catalysts simultaneously. In order to test and verify the system, four kinds of harmful gas were examined in our study, including carbon monoxide, acetone, chloroform and toluene.2.2.2.A multi-sensor image fusion system has a broad spatial and temporal coverage area, excellent target resolution capability, good fault tolerance ability, excellent reconstruction and system detection performance and high measurement dimensions. They were first used in military target detection and recognition. At present, multi-sensor image fusion technology has a variety of applications in air traffic control, surveillance, robot vision, harbor high speed transport driving, natural resources, weather forecasting and remote testing. Therefore, multi-sensor image fusion technology has developed rapidly, and the aim is to collect more information from a number of single sensors, and supplementary information could be merged into a new data set . StudiesIn our experiments, the characteristics of the CTL-based array performance for carbon monoxide, acetone, chloroform and toluene sensing were investigated under optimal conditions. Considering the fact that the fused images were not natural, a revised region-based color mapping method was employed to render the multi-sensor images . Experim2.2.3.PCA was used to classify the harmful gases and the results of nine sensor units for four chemicals were obtained. During our experiments, carbon monoxide, acetone, chloroform and toluene underwent five repeated tests under optimal conditions. Two PCs accounted for 97.60% of the total variance . In the test process, the acquired images were first converted by the image digitizer and input into an appropriate buffer. Then, according to the operator's instructions, the computer calls the image processing program in the library. After image processing, the computer generated output images pixel by pixel, they were transmitted into a cache or another actuating mechanism. Finally, the processing results can be recorded by the recording equipment.3.3.1.To evaluate the correlation between catalytic activity and CTL response, nine types of catalyst see  with dif2/Fe3O4 (1/3) has the highest CTL intensity, the spot of La2O3 (1/1) gives the weaker intensity, whereas the weakest one is BaCO3 (2/2). The conversion coefficient of carbon monoxide, acetone, chloroform and toluene for these three catalysts is 0.99. In conclusion, a good correlation between carbon monoxide, acetone, chloroform and toluene conversions can be obtained, so qualitative results for the catalytic sensitivities of those sensing materials for carbon monoxide, acetone, chloroform and toluene can be acquired from the CTL-based array images. In addition, the sensor array exhibits sensitive and stable CTL responses to the four compounds, and the relative CTL intensity increases with their concentrations. For example, responses of chloroform on the sensor utilizing the Au/La2O3 nanomaterial are shown in R = 0.9978). The quantitative analysis of this system indicates that it can be applied to quantify the concentrations of harmful gases according to the reaction intensity.The CTL intensities change with different metal catalysts, total metal loadings and ratio of bimetallic catalysts. Taking the catalysts at a metal loading of 1.0% as examples, on average, the spot of SiO3.2.2O3 nanomaterial is shown in The relation between CTL spectra wavelength, mean CTL intensity and S/N ratio for the four types of gases on the Au/La3.3.In optimizing the CTL-based sensor array, temperature is an important factor which must be taken into account, because the catalytic reaction is temperature dependent. Different temperatures may lead to different luminescence efficiencies during the course of discriminating one compound from another, which might have similar chemical properties. As shown in In regard to chloroform and toluene, patterns with a relatively weak spot brightness were obtained at 180 °C. When the temperature was increased to 240 °C and 280 °C, the brightness of the spots on the patterns was sufficient to differentiate between these four compounds. In our research, 240 °C was chosen as the optimal working temperature for detection and recognition of carbon monoxide, acetone, chloroform and toluene gases. The results confirm that different patterns can be obtained at different working temperatures which may contribute to distinguishing harmful gases.3.4.2O3 sensor unit were collected every 2 h. The single sensor exhibited good stability and durability when we continuously injected 1000 ppm carbon monoxide for 100 h. The sensor response intensity variation was limited to ±10%. As to the sensor array, the CTL patterns of acetone during 0–100 h was investigated. Most sensor units show no significant differences in CTL response. However, the response intensities on SiO2/Fe3O4 (1/3) and BaCO3 (2/2) suffered a slight decrease after 100 h.In our work, the stability of a single sensor unit and the whole array were all investigated. We found that the CTL-based sensor array showed excellent stability and durability toward carbon monoxide, acetone, chloroform and toluene. The results were obtained by testing the four kinds of common possible harmful compounds under the optimal conditions. For example, the CTL intensities of Au/La3.5.Selectivity is the ability of the system to distinguish one analyte from another, which is an important criterion in selecting a sensor array. In 4.2O3, SiO2, MgO, Al2O3, CeO2), decorated nanoparticles  and carbonates (BaCO3). They were selected and carefully synthesized. Secondly, distinct CTL patterns for the four types of harmful gas were obtained. Therefore, the harmful gases could be successfully recognized by the PCA method. Thirdly, the optimal conditions were determined: 420 nm was taken as the approximate optimal wavelength, 240 °C was chosen as the optimal working temperature, and the gas flow rate was 200 mL/min. In our experiments, characteristics of the system were investigated under optimal conditions. Fourthly, experimental results showed high sensitivity and long-term stability of the array, combined with simplicity, making our system exhibited a promising application. Finally, a good linear correlation between gas concentration and CTL intensity was verified, which indicated that the CTL intensity can be used in the evaluation of harmful gas concentrations.Firstly, a novel CTL-based sensor array consisting of nine types of catalytic materials was developed for the detection and recognition of harmful gases including carbon monoxide, acetone, chloroform and toluene. The sensing materials were composed of nanosized metal oxides (La5.2, Y2O3 and Mn3O4, that could be integrated into our system. In addition, improving the image fusion method maybe contribute to develop an improved CTL sensor array, and we will attempt to implement a color image fusion algorithm based on the Curvelet transform [Our approach has good potential to develop a CTL sensor array for analysis of other harmful compounds. There are many efficient sensing materials have been developed for gas sensors, such as Au/ZnO, SnOransform , which i


Systemic Lupus Erythematosus (SLE) typically affects females at far greater rates than males; however male SLE patients often have more severe disease than females. The gender disparities have been reported in clinical manifestations and in serological and hematological indices as well. In particular, SLE complicated with nephritis is more frequent in men than women, and several groups identified male gender as a risk factor for progression to renal failure. The specific differences in pathogenesis amongst genders have yet to be conclusively defined, though genetic, hormonal, and immune responses have been analyzed thus far. Further research is warranted to further elucidate these differences and permit the development of gender-tailored treatment regimens. Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can potentially cause inflammation and damage to any organ system. There are multiple genetic, hormonal, and environmental factors that are known to influence the development and nature of the disease. SLE is characterized by periods of high activity alternating with periods of remission and typically presents in females of childbearing age. During these reproductive years, the ratio of females to males is nine to one, with a lower ratio seen before puberty and a decline later in life. The increased rate of SLE in females implicates hormones as essential in disease manifestations, and this influence of sex hormones is also seen in animal models of the disease. Typically, in most mouse models, females have worse outcomes, and administration of estrogens exacerbates while androgens ameliorate disease . Despite the noted relationship of estrogens and increased autoimmune diseases in females, there is a growing body of the literature reflecting both different disease manifestations and a difference in severity of SLE in males versus females. Approximately 4% to 22% of SLE patients in reported series are male, and this number increases to 30% in studies regarding familial aggregation [The LUpus in MInorities, NAture versus nurture (LUMINA) cohort is a well-known multiethnic US Cohort consisting of Hispanic, African American, and Caucasian patients. To further understand the impact of gender on manifestations and outcome of SLE, researchers in the LUMINA Study Group compared disease activity in males versus females by the SLAM (Systemic Lupus Activity Measure) and damage accrual by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/SDI) at baseline and at the last visit. In addition to the above disease indices, socioeconomic/demographic, clinical, and serological features were compared for this study . P = 0.085) and positive lupus anticoagulant antibody (LAC) in males , but other antibodies occurred at comparable rates. Shorter disease duration at baseline, higher SDI at any time, and LAC at any time were factors independently associated with SLE in men (P = 0.014) and positively associated with damage over the course of disease as measured at the last visit . This study identified male gender as a risk factor for accelerated damage in SLE, in addition to reflecting differences in severity and manifestations of SLE by gender [Of the 618 LUMINA patients enrolled at the time of the study, 555 were female, 63 male. Caucasians were overrepresented amongst males. Poverty was less frequent, while smoking and alcohol use more common in males. Males in larger numbers experienced more difficulty in access to health care, but they showed more adequate illness-related behaviors at both points in time. These “illness-related behaviors” were measured using the Illness Behavior Questionnaire (IBQ), which assesses maladaptive responses to illness, including hypochondriacal responses, denial, and changes in affect. The IBQ was designed to indicate the extent to which these behaviors explain exaggerated response to health issues [E in men . MusculoRenal disease in SLE is a source of major morbidity and mortality; it develops in approximately 60% of patients with SLE, with a reported 5–22% of these patients progressing to end-stage renal disease requiring dialysis or transplant . MultiplLu et al. reviewed the existing literature published from 1975–January 2009 using the PubMed database to identify potential clinical characteristics in male lupus. Renal involvement was frequently more common in the studies reviewed, in both adult and pediatric SLE populations. In some, DPGN, the class with typically the poorest prognosis, was seen as the predominant finding on biopsy in males. Increased risk of renal failure and ESRD were also observed amongst males in greater numbers in various papers reviewed [Of the patients in our own institution participating in the Einstein Lupus Cohort, approximately 300 SLE patients have been entered into the registry, of which 35 (11.7%) are males. Of the male patients, 16 (47%) have renal disease, whereas around 33% of the female patients have renal disease. Forty-one (46%) females have proliferative nephritis (class IV or mixed IV and V), 26 have class III or mixed III and V. Biopsy data on the remaining female patients is unavailable. Eight male patients (50%) have proliferative nephritis; seven have class IV, one with mixed class III and IV. Three males have mixed class III and V, two male patients class III. Two patients have pure membranous disease (class V) and one did not have a biopsy . Our num Several groups have analyzed the clinical expression and outcomes of SLE in males in different ethnic populations and geographic regions. To evaluate whether male patients in their local Chinese population had differences in clinical features at diagnosis, course of disease and features, rate and severity of disease relapses, organ damage, and cumulative damage scores, Mok et al. performed a retrospective review of 51 male patients and 201 female patients at the Rheumatology and Nephrology Clinics of the Queen Mary Hospital in Pokfulam, Hong Kong [The above observation that disease course of SLE and male nephritis, aside from reduced GFR, was not different from males to females, differs from various other reports including another study of Acute Kidney Injury (AKI) in Chinese patients with lupus nephritis from a single center at the Peking University. AKI was defined as the presence of any one of the following items: an abrupt (within 48 hours) reduction in kidney function currently defined as an absolute change in serum creatinine of more than or equal to 0.3 mg/dL; a percentage increase in serum creatinine of ≥50% (1.5-fold from baseline); or a reduction in urine output (documented oliguria of less than 0.5 mL/kg per hour for more than 6 hours). AKI was previously identified as a risk factor for progression to ESRD. However, little was known about the patient characteristics of these patients or that gender may be a risk factor for AKI. The clinical, laboratory, renal histopathology, treatment, and outcome data were retrospectively collected and compared between lupus nephritis patients with and without AKI. The impact of AKI on renal outcome was evaluated . P < 0.001). The mean value of serum creatinine was 3.82 ± 2.59 mg/dL upon diagnosis. Most patients had hematuria (90.9%) and leukocyturia (71.2%). More than half of the patients presented with nephrotic syndrome (68.2%), with the amount of urine protein between 0.76 and 21.04 g/24 h (mean 6.57 ± 4.36). Regarding the pathological classification of lupus nephritis, the proportion of class IV was significantly higher (P < 0.001), and the proportion of classes III and V was significantly lower in the AKI group (P < 0.001 for both). In the AKI group, there was a significantly higher score of the total activity indices, endocapillary hypercellularity, cellular crescents, karyorrhexis/fibrinoid necrosis, subendothelial hyaline deposits, interstitial inflammation, leukocyte infiltration, the total chronicity indices, tubular atrophy, and interstitial fibrosis. In comparison with the non-AKI group, patients with AKI had significantly higher proportions of serositis (P < 0.001), neurologic disorder (P = 0.026), anemia (P < 0.001), thrombocytopenia (P = 0.013), and nephrotic syndrome (P = 0.011), but significant lower serum C3 (P < 0.001). The SLEDAI scores, renal pathological activity indices and, chronicity indices were significantly higher in the AKI group . Among 322 patients with renal-biopsy-proven lupus nephritis, 66 (20.5%) were identified as AKI. Male predominance was observed in patients with AKI (P < 0.001). In the AKI group, patients with crescentic glomerulonephritis and thrombotic microangiopathy had the worst renal outcome. AKI was an independent risk factor for renal outcome along with male gender, age, activity index score, presence of crescents, chronicity score, interstitial inflammation, glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis. The findings were consistent with the previous studies where mostly male lupus patients presented with more severe renal involvement and poorer outcome than female lupus patients, in clinical manifestations, laboratory characteristics, pathological features, and outcome of patients with AKI [Regarding outcome, the AKI group had a significantly poorer renal outcome compared with non-AKI group . At onset, men more frequently showed constitutional symptoms and a higher prevalence of neurologic manifestations . During disease course, renal disease, characterized by persistent proteinuria and/or cellular casts, was significantly higher in males , as was hemolytic anemia. Males more frequently had leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia, IgG anticardiolipin antibodies, and low C3, along with any form of cardiovascular manifestation , particularly arterial hypertension. Although not statistically significant, mortality was also higher in men [The Grupo Latinoamericano de Estudio del Lupus (GLADEL) started in 1997 as a multinational inception prospective cohort in Latin American centers having expertise in the diagnosis and management of SLE. The data from the first 1214 patients was incorporated in a computer database available to all groups and interconnected among them. M. A. Garcia et al. used the data to analyze the influence of gender in the disease pattern and prognosis in a prospective cohort of SLE patients from 34 centers in nine Latin American countries: Argentina, Brazil, Colombia, Cuba, Chile, Guatemala, México, Peru, and Venezuela [P = 0.004) and vascular thrombosis occurred at significantly higher rates in males. The rate of nephrotic syndrome  and the presence of dsDNA antibodies were significantly higher in males, as was the use of moderate-to-high doses of corticosteroids. Diffuse proliferative nephritis was the most common biopsy finding in both groups. Although there was no difference in mortality from all causes, SLE-related mortality was higher in the male group. The use of cytotoxic agents, dialysis, and renal transplantation was higher in the male group, though not statistically significant. Extrarenal manifestations more prevalent amongst males included CNS involvement, osteonecrosis, and severe cardiopulmonary disease.Molina et al. had found similar results in an earlier cross-sectional study of 107 Latin American male patients compared to a group of 1,209 Latin American female patients with SLE . In thisP = 0.002, OR = 2.806, 95% CI = 1.462–5.382). Specific details about class of nephritis or progression to ESRD and dialysis were not provided. The rates of thrombosis were 20.3% versus 4.7% , and stroke 8.5% versus 0.9% . During the 5-year followup, positive associations were noted between male gender and the incidence of tendonitis, myositis, nephropathy, and infections, particularly of the respiratory tract [Gender differences in SLE and nephritis were studied by two separate groups in Greece. The more recent retrospective study by Stefanidou et al. sought to analyze the prevalence of the most relevant clinical features of SLE in a sample of male patients as well as the incidence of the main causes of morbidity in a 5-year period after the diagnosis. Another goal was to investigate the impact of gender on expression and morbidity of SLE. Data were collected from the medical records of 59 male and 535 female patients with SLE who were diagnosed at the hospitals in the region of Thessaloniki. Several differences in the expression and morbidity of the disease were found in relation to the gender of the patient. Male patients had a higher prevalence of thromboses, nephropathy, strokes, gastrointestinal tract symptoms, and antiphospholipid syndrome when compared with female patients, but tended to present less often with arthralgia, hair loss, Raynaud's phenomenon, and photosensitivity as the initial clinical manifestations. The rates of nephropathy were 27.1% in males versus 16.1% in females , while 68 were male 14%). There were no significant differences in the mean age at presentation, mean age at disease onset, duration of the disease, or in duration of followup between men and women. At the time of diagnosis, there were no major differences in major organ involvement; during followup, men had a greater frequency of renal involvement in younger patients. Eight men (14%) and 25 women (7%) developed chronic renal failure, while 3 men (5%) and women (1%) developed end-stage renal disease. No other major organ differences were observed between genders [%. There The study of SLE within the United States Military presents a unique opportunity for examining clinical variables in the period before diagnosis. In addition, the demographics of the United States Military increase the expected proportion of male SLE patients. All military personnel have readily accessible health care and are required to receive regular physical exams, minimizing the impact of health care disparities and, to a lesser extent, of socioeconomic and cultural differences. The US Department of Defense serum repository contains samples from active duty personnel at entry into the military and, on average, every other year thereafter. Arbuckle et al. used this data to make comparisons between demographic, serologic, and clinical manifestations, as well as to identify factors associated with the manifestations of disease during the clinical period after the initial presentation to diagnosis of lupus. A cohort was assembled of 130 individuals diagnosed with SLE while on active duty in one of the United States uniformed services, with the goal of identifying potential subsets within the patient population [P = 0.001; OR = 9.2). Manifestations at presentation and during followup were identified for AA males and compared to others  in order to assess for clinical variables that might contribute to the rapid onset observed in AA males. AA males had more anti-RNP antibodies, developed more nephritis and had less cutaneous manifestations than AA females and EAs. African American males were much more likely to present with nephritis, pleuritis, and/or seizures than others [Sixty-five of the patients were women; among the entire population 62% were African American (AA) and 26% were European American (EA). Asians and Hispanics comprised three and 9%. Individual gender subgroups contained sufficient numbers to permit separate analyses for AA and EA men and women. No difference in the time of the occurrence of the first criterion to diagnosis was based upon ethnicity alone; however, the time from this first manifestation to diagnosis was significantly shorter for males when compared with females. Evaluation of AA males in whom the diagnosis was made 0.17 years after the presence of their first clinical criteria suggests that this difference was due almost exclusively to AA males. Eighty-seven percent of AA males met SLE diagnostic criteria less than six months after their initial presentation criteria compared with 42% of AA females  and 1822 women .The mean followup was 6.02 years (range 0–23.73). Men were more likely than women to have hypertension, thrombosis, renal, hematological, and serological manifestations. Specifically increased in males were lymphopenia, positive anti-Sm, direct Coombs, lupus anti-coagulant, low C3, and anti-dsDNA. Men experienced increased rates of end-organ damage including neuropsychiatric, renal, cardiovascular, peripheral vascular disease, and myocardial infarction, and to have died. Women were more likely to have malar rash, photosensitivity, oral ulcers, alopecia, Raynaud's phenomenon, or arthralgia .In the pediatric SLE population, as previously stated, the gender difference in numbers of patients is much reduced, to a ratio of three to one females to males before puberty. Several studies have reported that children have often an aggressive clinical course with more frequent renal involvement as compared to adults. Boys were reported to have a higher prevalence of severe renal disease and poorer outcome, but other reports did not confirm these findings . Al-MayoAs above, sex hormones are probably partly responsible for the higher occurrence of autoimmune disorders given the female predominance in autoimmune diseases. However, studies have found that sex hormone levels in patients with autoimmune disorders are not significantly different from patients without autoimmune disorders, indicating that other gender-associated differences including hormone regulation and effects on cytokine production, along with chromosomal factors, contribute to the high female predominance in these diseases compared with men . Thus, tα/β) that are expressed on most immune cells. ERs are nuclear hormone receptors that can either directly bind to estrogen response elements in gene promoters or serve as cofactors with other transcription factors. ERs have prominent effects on immune function in both the innate and adaptive immune responses. Genetic deficiency of ERα in murine models of lupus results in significantly decreased disease and prolonged survival, while ERβ deficiency has minimal to no effect in autoimmune models [Estrogen's primary effects are mediated via estrogen receptors alpha and beta  [γ (INFγ), TNFα, TGFβ, interleukin (IL)-1, IL-5, IL-4, and IL-10 production. Estrogen causes a proliferation of M2 macrophages, and myeloid-derived suppressor cells, further amplifying the Th2 immune response [ERls (DCs) . Estradiresponse . Estrogeresponse . Regarding DCs, Oertelt-Prigione found that exposure of immature murine DCs to estrogen increased their IL-6, IL-8, and MCP-1 production, but most importantly enhanced their stimulatory capacity on T lymphocytes, and another group demonstrated estrogen's role in enhancing the differentiation of DCs from bone marrow in vivo. Estrogen-driven upregulation of MHC II in the dendritic cells, enhancement of proinflammatory cytokine production, and an interaction between estrogen and MHCII expression regulation have also been confirmed in animal models . α KO genotype was bred onto three different murine lupus-prone strains, NZB/NZW f1, MRL/lpr, and NZM2410. In each of these three strains, the lack of ERα significantly attenuated disease. In NZB/NZW mice, the lack of ERα resulted in decreased autoantibody levels, while in NZM2410 and MRL/lpr mice, autoantibodies, if anything, were increased; the primary impact of ERα deficiency appeared to be on the response of the kidney to immune injury. When used in murine models of lupus, ER inhibitors were reported to have beneficial effects on lupus disease expression [Further evidence of sex hormones influence on systemic autoimmunity is derived from lupus animal models (NZB X NZWF1). In this model females develop disease earlier than males and die at younger age. Oophorectomy delays the disease onset while castrated males suffer of early and more severe disease; treatment with estrogens and prolactin causes early mortality. In comparison, mice treated with the estrogen receptor antagonist tamoxifen have a mild disease and a longer life . In a repression . Additional details about estrogen-induced modulation of cytokine production in SLE mediated by the estrogen receptor and of the various aspects of estrogen receptor signaling in this disease, estrogen receptor subtypes, their structure, and the mode of action of estrogens by gene activation and via extranuclear effects are outlined in a recent review by Kassi and Moutsatsou .P = 1.2 × 10−5)) and more likely to have thrombocytopenia ) [P = 0.0010; rs1270942: OR male-female 1.40 (95% CI = 1.16 to 1.69), P = 0.00046). This was also the case for an SNP in IRF5 , P = 0.039). There was no difference in the risk allele frequencies in the control group between men and women . As SLE affects more females than males, it is unexpected that the disease in males would be more severe. Given this predominance of the disease in females and its association with higher estrogen in both males and females, Hughes et al. sought to clarify why affected men often experience more severe disease by examining sex-specific genetic effects among SLE susceptibility loci. The group of male patients in this study was noted to have twice the risk of renal disease ) . They inβ estradiol, is capable of inhibiting inflammatory and proapoptotic processes and protecting the renal tissue. In contrast, the male hormones, testosterone and dehydroepiandrosterone, have the opposite effect. Hormonal manipulation by male or female castration changes the course of renal disease progression and confirms the influence of the sex hormones. Female gender is therefore considered a protective factor in many kidney diseases, such as primary glomerulonephritis, autosomal dominant polycystic kidney disease (ADPKD), and hypertensive nephropathy [In many clinical and experimental scenarios, the incidence and the rate of progression of non-lupus-related renal diseases are influenced by multiple gender-dependent factors, such as kidney and glomerular size, differences in glomerular hemodynamics, and direct effects of sex hormones on renal tissue and signal pathways such as the renin-angiotensin-aldosterone system and signal molecules  . It has hropathy . Studies in patients with chronic kidney diseases have also shown that men have a more rapid disease progression and that with age, men exhibit greater decrements in renal function and increased glomerular sclerosis than women . Women wAlthough the gender effect of dimorphism in lupus nephritis development has been often attributed to sex hormones as above, XXY males have nearly a 14-fold higher risk of developing SLE than 46 XY males, indicating that X-linked genes may also be risk factors for SLE in humans .TLR8 encode proteins that play critical roles in pathogen recognition and activation of innate immunity; they recognize endogenous RNA-containing autoantigens and when stimulated promote the expression of type I IFN, a pivotal cytokine in the pathogenesis of SLE. Animal models have demonstrated a connection between X-linked gene overexpression and TLR7. The BXSB strain of mice spontaneously develops an autoimmune syndrome with features of SLE; males are affected much earlier than females. Genetic analysis of the F1 hybrids of male BXSB mice with other lupus-prone mice demonstrated that the accelerated development of SLE in male BXSB mice is linked to the Y chromosome of the BXSB strain. This genetic abnormality present in BXSB Y chromosome has thus been called Yaa, Y-linked autoimmune acceleration [Located at Xp22.2, Toll-like receptor 7 and its functionally related gene leration . The Yaa mutation was shown to be a consequence of a translocation from the telomeric end of the X chromosome and onto the Y chromosome . Based oP = 4.1 × 10−4). Their data established a functional polymorphism in type I IFN pathway gene TLR7 predisposing to SLE, especially in Chinese and Japanese human male subjects [Amano et al. additionally demonstrated that the Yaa mutation causes defective development of marginal zone B cells in BXSB mice, suggesting a role for the marginal zone B cells in the generation of pathogenic autoantibodies in SLE . Shen etsubjects .The impact of gender in SLE renal disease has been assessed thus far, mostly with chart reviews and retrospective analyses. In order to further identify and clarify the true and significant differences in pathogenesis, prognosis, and long-term outcome, more systematic and prospective studies should be undertaken. Both nonrenal  and rena


Mitochondria are key organelles in the cell, hosting essential functions, from biosynthetic and metabolic pathways, to oxidative phosphorylation and ATP production, from calcium buffering to red-ox homeostasis and apoptotic signalling pathways. Mitochondria are also dynamic organelles, continuously fusing and dividing, and their localization, size and trafficking are finely regulated. Moreover, in recent decades, alterations in mitochondrial function and dynamics have been implicated in an increasing number of diseases. In this review, we focus on the relationship clarified hitherto between mitochondrial dynamics and cancer, neurodegenerative and neuroinflammatory diseases. In regard to the cell life, mitochondria produce most of the ATP necessary to the cell through oxidative phosphorylation, and they are involved, among the others, in TCA cycle, fatty acid metabolism, hemesynthesis, and gluconeogenesis. As regards the cell death, mitochondria are involved in Camodeling –3. Moreover, mitochondria are highly dynamic organelles that can fuse and divide, forming an interconnected network or fragmented units inside the cell, according to different stimuli impinging on the fusion/fission machinery, represented by the mitochondria shaping proteins: MFN1, MFN2, OPA1, regulators of fusion, and DRP1, FIS1, MFF, and MIEF1, which modulate fission  see Fig.2+ homeostasis and signalling [c, which then interacts with APAF1 and caspase 9 forming the apoptosome, whose activation results in the amplification of cell death signals [MFN1 and MFN2, two dynamin-related GTPases, are the main regulators of mitochondrial fusion at the level of outer mitochondrial membrane (OMM). They can interact, forming homo- and heterodimers; after conformational changes led by the hydrolysis of GTP, they force the OMM to fuse . Interesgnalling . OPA1, agnalling . OPA1 ha signals , 9. Othe signals , the Pho signals , and Pro signals , the latIn summary, the pleiotropic mitofusins (MFN1 and MFN2) and OPA1 are the main regulators of the mitochondria fusion machinery. Although steps forward have been made, some points of this mechanism still remain to be clarified; in particular, how the IMM fuses and how its fusion is coordinated with events of the OMM fusion. The fission machinery is based on DRP1, FIS1, MFF, and MIEF1. DRP1 is a large GTPase protein , which iThe scenario of mitochondrial fission is becoming more complex, taking into account the different roles proposed for MFF, MIEF, and FIS1. MFF has recently been shown to be an adaptor of DRP1 on the OMM , whereasIt has also been suggested that mitochondrial fission events predominantly occur at the contact sites between ER and mitochondria, specifically where some ER tubules cross over and wrap around mitochondria. Interestingly, DRP1 and MFF localize at these contact sites . New stuIn summary, the fission machinery depends on the activation and translocation of DRP1 to the OMM, where it interacts with some other components, not clearly defined, that take part to the modulation of mitochondrial fragmentation. Changes in mitochondrial morphology have been related to alterations in mitochondrial function, transport, location, and quality control. Mitochondrial damage, for example, induces fission, which, in turn, allows mitochondria to be engulfed by the autophagosomes and then degraded .Autophagy represents a cellular self-degradation process involved in the degradation of bulk cytoplasmic components, proteins, or entire organelles in basal or nutrient depleted conditions. This process is also described as macroautophagy and is different from the selective autophagy. The latter is responsible for selective degradation of damaged and dysfunctional organelles, and, thus, it represents the quality control system for mitochondria . In casein vivo genetic ablation of fusion , or fisout mice ) proteinAccording to the classification of the hallmarks of cancer by Hanahan and Weinberg , a cell C. elegans, is able to interact with MFN2-inducing mitochondrial fusion [L promotes instead fission stimulating the DRP1 GTPase activity [Bak −/−Bax −/− cells have an elongated mitochondrial network [Escaping death signals is one of the first characteristics of a tumoral cell. Bcl-2 family proteins play an important role in balancing life and death signals  convergil fusion . BCL-XL activity . The proactivity , indeed, network . Interes network . Finally network . ψ), is necessary for mitochondrial fusion [Another feature of tumoral cells is the already mentioned shift from the production of ATP by oxidative phosphorylation to a glycolytic phenotype despite the presence of oxygen . It is nl fusion , 50.It has been shown that mitochondria undergo fragmentation during the S and M phase of the cell cycle to allow a limitation of the mutation rate during DNA replication, through a temporary decrease of oxidative phosphorylation (which is the main source of ROS). Such fragmentation is also necessary for an equal segregation of mitochondria between the daughter cells , 52. ThiTo continue this overview, ROS can be considered as both initiator factors of the tumor (inducing genome and mtDNA mutations) and enhancing factors giving a higher rate of proliferation to the cells , 55. ROSInterestingly, clinical studies of lung adenocarcinoma reveal a role for DRP1, independent of the mitochondrial morphology. In this tumor, DRP1 is overexpressed, but is sequestered in the nucleus by hHR23A, so avoiding its localization on mitochondria and conferring resistance to cisplatin . A centrerv-1-like (GERF)-dependent DRP1 downregulation, which leads to mitochondrial elongation and an enhanced cell viability [In a more general way, cancer cells share characteristics with stem cells, in particular regarding mitochondrial morphology, localization, function, and mtDNA content . Of noteiability .Finally, in lymphocytes mitochondria fission and relocalization to the uropod are necessary for the polarization and chemotaxis of these cells , so unraBefore starting the examination of different pathologies directly related to mitochondrial dynamics failure or imbalance see , we woulKinesin1 [Htt (the gene of HUNTINGTIN protein) is able to block mitochondrial movement [α-SYNUCLEIN, LRRK2, and PARKIN, to disrupt the microtubule network in the cell [Neurons, especially motor neurons, are characterized by long axons up to more than one meter at the end of which synapses exert their role in cellular-cellular communication. The resulting importance of mitochondrial anterograde transports to the synapses (to ensure ATP production necessary for neurotransmitters vesicles to be discarded ) and of Kinesin1 . That saKinesin1 , 66, guaKinesin1 , 68. NotKinesin1 , 69, 70.movement  and causmovement ; in Parkmovement , as wellthe cell –76. 2+-signalling implications has emerged [2+ overload in mitochondria in physiological condition and revealing, thus, an unexpected connection with mitochondrial trafficking. In fact, MIRO is a calcium-binding protein; it has been proposed that only in calcium unbound state  is it able to interact with MILTON, so allowing movement of mitochondria [2+ homeostasis, due to abnormal ER-Mito crosstalk, results in impaired mitochondrial movement and consequently in neurodegeneration [β, a constituent of extracellular neurite plaques in AD, is abundant in MAMs, contributing to interorganellar dysfunctions [In recent decades, a functional role for mitochondria-ER interactions and Ca emerged . The sitchondria . Thus, aneration . Moreoveunctions . Alteredunctions , and forunctions .in vitro. Briefly, loss of Δψ induces stabilization of PINK1 on the OMM and allows PARKIN recruitment on mitochondria. This, in turn, leads to ubiquitination of mitochondrial substrates and their interaction with p62 and LC3 so as to induce the engulfment of mitochondria inside the autophagosome [The role of mitochondrial quality control is becoming increasingly prominent in the explanation of neurodegenerative diseases such as Parkinson disease (PD) and others. A general mechanism of mitochondrial quality control relies on the PINK1/PARKIN pathway, deeply studied hagosome , 25. MFNhagosome  and thenhagosome . Others hagosome .Coming back to the pathologies, in this paragraph, we will focus on the links between some of them and the mitochondrial dynamics.β (Aβ) plaques and tau-containing intracellular neurofibrillary tangles in the brain, these leading to progressive neuronal death. From a morphological point of view, neurons expressing amyloid protein precursor (APP), or Amyloid β, show abnormal levels of mitochondrial shaping proteins with downregulation of MFNs and OPA1 and upregulation of DRP1 and FIS1 [β interacts with DRP1 [δ (PKC δ) [The main clinical feature of Alzheimer disease (AD) is the accumulation of extracellular deposits of amyloid and FIS1 , 109. Amith DRP1 , promotiith DRP1 , 111. Tiith DRP1  and reduith DRP1 . Interesith DRP1 , while a (PKC δ) , as it hin vivo models of HD. In addition, 3-nitropropionic acid, an irreversible inhibitor of complex II, has been shown to induce mitochondrial fragmentation and HD-like symptoms in rats and mice [A mitochondrial connection is emerging also in Huntington's disease (HD); mitochondrial succinate dehydrogenase , aconitase defects , and mtDand mice . Of noteand mice  with an and mice . Mutant and mice . This phand mice –120.α-synuclein, Pink1, Parkin, DJ-1, and Leucine-rich repeat kinase 2 (LRRK2) as commonly mutated genes in Parkinsonism. α-SYNUCLEIN and LRRK2 have been proposed as playing a role in microtubule organization and, thus, in mitochondrial trafficking [ψ is obtained by treating cells with high concentrations (or for long terms) of the protonophores CCCP or FCCP. A common challenge in the next future will be the identification and the use of more physiological stimuli to induce mitochondrial damage, and mitophagy, to better mimic the in vivo mechanism of pathophysiology of neurodegenerative diseases. By this way, it will be possible to clarify some of the discrepancies remaining in the field such as, for example, the differences observed so far for the PINK1/PARKIN functional interaction in various cell lines; or considering the loss of Δψ  as the only event triggering mitophagy, another point highly debated and controversial to date.Independent studies identified fficking , 75. PINfficking , 25, as fficking , 122, dofficking . Also infficking , 85. Thefficking . The appfficking . This suDJ-1 knockout presents mitochondrial fragmentation [A mouse model of entation , increasentation . Complexentation , 126, soIn the 20% of patients affected by an autosomal dominant form of amyotrophic lateral sclerosis (ALS), a gain of function mutation in SOD1 has been detected . DefectsOpa1 mutations are responsible for the autosomal dominant optic atrophy (ADOA) [y (ADOA) , 95. Cony (ADOA) , 130. Ony (ADOA) , 97. Whay (ADOA) , 130. Iny (ADOA) , in liney (ADOA) .Parl  has, as a primary cause, mutations in mtDNA . Recentlleavage, ) has beeleavage, .MFN2 is involved in the most common form of the autosomal dominant axonal Charcot-Marie-Tooth (CMT2A) disease . MoreoveMfn2 knock-out systems, death of Purkinije cells has been observed, confirming a role for MFNs in protecting against lack of mtDNA and dysfunction of mitochondria in the cerebellum [In addition, in a mouse model of apoptosis-inducing factor (AIF) deficiency, MFN1 levels are decreased in the cerebellum and are accompanied by death of Purkinije cells . This phrebellum .In the last decade, a link between neurological and lymphatic aspects has emerged in schizophrenia . RecentlTo conclude, neurons rely on mitochondrial distribution, function, and dynamics to allow synapses and dendrites formation, energy supply, and quality control. The main properties of neurons constitute risk factors themselves if we consider the effects of mitochondrial dysfunctions. First, they are cells highly demanded in energy; second, they have long processes connecting the soma to synapses and dendritic spines; third, they are long-lived postmitotic cells. Although knowledge is increasing about mitochondrial role in neurodegenerative diseases, much remains to be elucidated, in particular, why different subpopulations of neurons are more vulnerable to mitochondrial fusion/fission imbalance and dysfunctions. Little is known about the link between mitochondrial dynamics and neuroinflammatory or autoimmune diseases. In this section we present correlations described to date with multiple sclerosis (MS) and type I diabetes, as examples for this category of diseases see . We thenOptic neuritis (ON) is a neuropathy characterized by demyelination of the optic nerve; it can be present by itself or as part of MS. Multiple sclerosis is an autoimmune disorder characterized by chronic demyelination of the central nervous system (CNS). The pathogenesis of MS is thought to involve self-antigen-reactive T lymphocytes that have the capacity to invade the CNS and to promote tissue damage.OPA1 mutation (S646L) ADOA has been shown to be associated with MS. This mutation leads to reduction of respiratory rates with lower ATP production [It is not rare to find mtDNA mutations and mitochondrial abnormalities in patients affected by ON . For insoduction , which ioduction . Interesoduction .β cells in the pancreas, clinically leading to increased glucose in blood and urine. Coronary endothelial cells from diabetic mice are characterized by fragmented mitochondria with a downregulation of OPA1 and an upregulation of DRP1 [β cells [phb-genetic ablation results in aberrant mitochondrial cristae structure and an increased apoptosis, dependent on increased proteolytic processing of OPA1 [Type I diabetes is an autoimmune disorder caused by autoimmune elimination of insulin-producing  of DRP1 . In addi[β cells . Interes of OPA1 . Moreove of OPA1 .2+ entrance and to avoid calcium-dependent T-cell inactivation [The importance of mitochondrial localization and activity in T cell function is well established. T cells are activated at the so-called “immunological synapse” between a T cell and an antigen-presenting cell (APC) . Mitochotivation . Moreovetivation . In recetivation , 149.c release [Mitochondrial fission, driven by FIS1 and DRP1, also contributes to the immune system tolerance and the tumor-immune escape in a galectin-1 (GAL-1)-dependent manner. GAL-1 sensitizes resting and activated T cells to FAS-mediated cell death program, which is characterized by mitochondrial dysfunctions, membrane potential alteration, mitochondrial fission, and cytochrome  release .It still remains to be elucidated whether or not mitochondrial dynamics play a crucial role in other important physiological processes in T cells.ψ loss and ROS production [Finally, CD47 can trigger cell death in a B lymphocyte leukemia. Also this apoptotic pathway is characterized by DRP1 translocation to mitochondria, which depends on chymotrypsin-like proteases, Δoduction . This laThe observations here presented suggest a prominent role for mitochondrial dynamics in a plethora of pathways from cell proliferation to resistance to apoptosis, from cell-energetic requirements to quality control mechanisms, from homeostasis to activation and movement of immune system cells. However our observations also suggest the potential for many new findings to come. The aim of future studies would, therefore, be to extend our knowledge of basic mechanisms underlying pathologies, and their relationship with mitochondrial morphology alterations. This, in turn, could make it possible to draw up novel strategies and treatments to improve the prognosis of an increasing number of patients.


PRSS1, SPINK1, CTRC and CFTR. For the purposes of the study, synonymous, intronic and 5'- or 3'-untranslated region variants were excluded from the analysis except where there was persuasive evidence of functional consequences. The remaining sequence variants/genotypes were classified into causative, contributory or neutral categories by consideration of (i) their allele frequencies in patient and normal control populations, (ii) their presumed or experimentally confirmed functional effects, (iii) the relative importance of their associated genes in the pathogenesis of chronic pancreatitis and (iv) gene-gene interactions wherever applicable. Adoption of this strategy allowed us to assess the pathogenic relevance of specific variants/genotypes to their respective carriers to an unprecedented degree. The genetic cause of ICP could be assigned in 23.7% of individuals in the study group. A strong genetic susceptibility factor was also present in an additional 24.5% of cases. Taken together, up to 48.2% of the studied ICP patients were found to display evidence of a genetic basis for their pancreatitis. Whereas these particular proportions may not be extrapolable to all ICP patients, the approach employed should serve as a useful framework for acquiring a better understanding of the role of genetic factors in causing this oligogenic disease. Idiopathic chronic pancreatitis (ICP) has traditionally been defined as chronic pancreatitis in the absence of any obvious precipitating factors  and family history of the disease. Studies over the past 15 years have revealed that ICP has a highly complex genetic architecture involving multiple gene loci. Here, we have attempted to provide a conservative assessment of the major genetic causes of ICP in a sample of 253 young French ICP patients. For the first time, conventional types of mutation (comprising coding sequence variants and variants at intron/exon boundaries) and gross genomic rearrangements were screened for in all four major pancreatitis genes,  Chronic pancreatitis, a persistent inflammation of the pancreas that results in irreversible morphological changes and impairment of both exocrine and endocrine functions, is a potentially life-threatening disease. In Western countries, alcohol abuse is the leading cause of chronic pancreatitis, accounting for approximately 70% of all cases. Other aetiological factors, including hyperparathyroidism, hypertriglyceridemia, duct obstruction, trauma, pancreas divisum, autoimmune pancreatitis and hereditary pancreatitis, are responsible for causing the disease in approximately 10% of patients. The remaining ~20% of cases, in which none of the abovementioned aetiological factors can be identified, have been collectively termed idiopathic chronic pancreatitis (ICP)  as compared with a sample of 514 French controls [4.9% (25/514)]. This finding concurs with that of the recent Rosendahl study [CFTR p. R75Q with SPINK1 p. N34S; only two of our seven heterozygous CFTR p. R75Q patients also carried a heterozygous SPINK1 p. N34S  were classified as causative, contributory or neutral in accordance with the combinations of the A, B and C category alleles (CFTR genotype whilst 23.7% (N = 60) carried a contributory genotype , OR 38.7; 95% CI 12 to 125.1).122 ICP cases were found to carry at least one contributory or causative genotype as assigned in this study   2.Of the 22 digenic pathological genotypes, 12 comprised a disease-causing genotype and a contributory genotype  of the 253 cases; to date, they have not been reported by other groups. Whether this is due to the absence of such events in other populations or simply due to the fact that they have not been sought in a methodical fashion is unclear. Third, and relevant to the ‘conservative’ nature of the study, it is worth pointing out that the intronic regions of the four major genes were not screened for mutations. Despite these limitations, we have demonstrated that a prerequisite for understanding the genotype-phenotype relationship in a complex disease such as ICP is not a simple variant number count but rather an overall assessment, made on an individualized basis, of the net effect of an oligogenic variant profile on the eventual risk of disease.Table S1Variants/genotypes reported in the current study.In columns B, C and D, the variants or genotypes classified variously as causative, contributory or neutral are given in red, blue and black, respectively. In column E, the CFTR alleles classified individually as severe, mild or associated with CFTR-related disorders, and neutral are in green, violet and black, respectively. In column F, x and xx indicate contributory and causative genotypes, respectively, with gene-gene interactions being taken into consideration. In column G, 1, 2, 3 and 4 refer to pathological PRSS1, SPINK1, CTRC and CFTR genotypes, respectively. See text for details.(XLS)Click here for additional data file.


Racial disparities in breast cancer survival have been well documented. This study examines the association of race/ethnicity and socioeconomic status (SES) on breast cancer-specific mortality in a large population of women with invasive breast cancer.We identified 179,143 cases of stages 1–3 first primary female invasive breast cancer from the California Cancer Registry from January, 2000 through December, 2010. Cox regression, adjusted for age, year of diagnosis, grade, and ER/PR/HER2 subtype, was used to assess the association of race/ethnicity on breast cancer-specific mortality within strata of stage and SES. Hazard ratios (HR) and 95% confidence intervals were reported.Stage 1: There was no increased risk of mortality for any race/ethnicity when compared with whites within all SES strata. Stage 2: Hispanics  in the lowest SES category had a reduced risk of mortality.. Blacks had the same risk of mortality as whites in the lowest SES category but an increased risk of mortality in the intermediate  and highest  SES categories. Stage 3: Hispanics  and APIs  in the lowest SES category had a reduced risk while blacks had similar mortality as whites. Blacks had an increased risk of mortality in the intermediate  and highest  SES categories.When analysis of breast cancer-specific mortality is adjusted for age and year of diagnosis, ER/PR/HER2 subtype, and tumor grade and cases compared within stage and SES strata, much of the black/white disparity disappears. SES plays a prominent role in breast cancer-specific mortality but it does not fully explain the racial/ethnic disparities and continued research in genetic, societal, and lifestyle factors is warranted. Breast cancer is the most common cancer in women residing in California, regardless of age or race/ethnicity -3 but thA wealth of studies have documented the many factors specifically associated with disparities of cancer care such as age, race/ethnicity, socioeconomic status (SES), access to health care, cultural, medical, and health provider issues -18. AddiOver 40 years ago, the California Cancer Registry (CCR) noted that breast cancer patients treated at private hospitals survived their cancer better than patients treated in public hospitals . ExpandiUsing the population-based CCR, we identified cases of American Joint Commission on Cancer (AJCC) stages 1–3 first primary female invasive breast cancer (ICDO-3 sites C50.0-C50.9)  diagnoseQuintile of SES was derived using data from the 2000 U.S. census. SES was assigned at the census block group level and based on address at time of initial diagnosis, as reported in the medical record. This area based composite SES measure was created through principal components analysis  and inclFor ease of presentation, in this study, we combined the lowest two quintiles 1 + 2 (lowest/least affluent) as well as the highest two quintiles 4 + 5 (highest/most affluent).The intermediate (3) remained intact.Race/ethnicity was classified into six distinct categories: White, African American or black, Hispanic, Asian-Pacific Islander (API), American Indian, and Hispanic plus other race. The race/ethnicity information contained in the medical record was obtained by patient self-identification, assumptions based on personal appearance, or inferences based on the race/ethnicity of the parents, birthplace, surname, or maiden name. The API category was derived from combining cases identified as Pacific Islander, Southeast Asian, Indian continent, Chinese, Japanese, Filipino, and Korean.Determination of Hispanic ethnicity was based on information from the medical record and computer-based comparisons to the 1980 U.S. census list of Hispanic surnames. Patients identified as Hispanic on the medical record as white with a Hispanic surname were classified as Hispanic. Cases identified as black or API and also identified as Hispanic were categorized as Hispanic plus other race. This classification resulted in six mutually exclusive categories: White, black, Hispanic, API, American Indian, and Hispanic plus other race.The details of documentation of estrogen receptor (ER) progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) along with age and stage at diagnosis, and tumor grade have been extensively described in our previous publications ,32,35,36The number of cases with missing data for ER, PR, HER2, race, grade, cause of death, and survival time were computed. Contingency tables were used to assess the distribution of missing data by race, and the distribution of demographic and tumor characteristics among SES strata.Cox proportional hazards modeling was used to determine time from breast cancer diagnosis to time of breast cancer-specific death for African Americans, Hispanics, and APIs, when compared with whites. All analyses were conducted separately for each stage because of the differences in prognosis of patients diagnosed in different stages. Separate models with and without SES were run to test whether SES confounded the association of race with mortality. The interaction between race and SES was then tested to determine if the affect of race on mortality varied among the levels of SES.Analyses were stratified by both stage and SES so that the risk of mortality for each race could be estimated for cases within each stage/SES stratum.All models were adjusted for age, ER/PR/HER2, grade, and year of diagnosis. Hazard ratios (HR) and 95% Confidence Intervals (CIs) were computed for all models. The HR represents the estimated risk of mortality for two people of the same age and tumor characteristic when one person is black, Hispanic, or API, and the other person is white.This research study involved analysis of existing data from the California Cancer Registry without subject intervention. No identifiers were linked to subjects. Therefore, the study was approved by Sutter Health Central Institutional Review Committee under the category "exempt".The initial data contained 181,090 cases of stages 1–3 first primary invasive breast cancer. Cases where race was identified as American Indian (n = 275), Hispanic plus other race (n = 517), or race unknown  were excluded, which resulted in 179,143 cases with complete data for year of diagnosis, age, race/ethnicity, stage, vital status, and SES. Tumor grade, ER/PR/HER2 status, and unknown cause of death were missing for 57,695 cases leaving 123,395 cases with complete data .Table The relationship between stage and SES was informative. For patients in the lowest SES category, 43.7% were stage 1, whereas 51.7% of patients within the highest SES category had stage 1 disease. For stages 2 and 3, with each increase in an SES category a decrease in the percent of patients was noted.A significantly higher percent of patients within the lowest SES category had the ER-/PR-HER2- and ER-/PR-HER2+ subtypes when compared with the highest SES category (Table The distribution of cases by race/ethnicity is shown in Table The ER+/PR+/HER2- subtype was the most common (57.2%), but variation by race/ethnicity was noted, especially between white (60.3%) and black patients (42.9%). Black and Hispanic patients had the highest percent of the triple-negative subtype, 25.5% and 16.3%, respectively. Whites had the lowest percent of patients among the four HER2-positive subtypes. This was especially noticeable within the ER-/PR-/HER2+ subtype, the molecularly defined HER2-overexpressing subtype, with whites having the lowest (5.5%) and API patients the highest (9.3%) percent.The majority of white patients (52.1%) presented in stage 1, compared with approximately 40% of both black and Hispanic patients presenting in this stage. A higher percent of black (15.9%) and Hispanic (15.7%) patients presented with stage 3 disease compared with white (9.9%) and API (10.7%) patients. Over 60% of white patients presented with the ER+/PR + HER2- subtype. Among black patients, 25.5% had ER-/PR-HER2- compared with only 11.3% of whites. African Americans, Hispanics, and API patients were diagnosed at a higher grade . SES reduced the effect of all race/ethnicities on mortality in all stages. The strength of the effect of SES was strongest for blacks in stage 1 where the HR was reduced 9.2% from 1.32 for blacks without inclusion of SES to 1.19 when included. The models that included the interaction between SES and race/ethnicity were statistically significant for stages 2 and 3 (p < 0.05) which indicated that the association of race with mortality was not the same for all levels of SES. Therefore models stratified by both stage and SES were more appropriate and these results are presented in Table Table For stage 3, in the lowest SES category, Hispanics and APIs had a reduced risk of mortality while blacks had similar mortality as whites. In the intermediate SES category, blacks had a 52% increased risk of mortality and a 53% increased risk in the highest SES category.For all stages, there was no black/white disparity in the lowest SES category. However, Hispanics in the lowest SES had better survival than whites in stages 2 and 3.Racial disparities in breast cancer treatment and outcomes have been previously well documented ,8,37,38.It remains difficult to completely separate and untangle the interplay among race/ethnicity, SES, and tumor biology, and determine their respective roles in breast cancer outcomes. This dilemma is evident from the conflicting results of studies investigating racial/ethnic disparities in cancer. Some have shown comparable outcomes after adjustment for sociodemographic factors if patients have equal access to healthcare -52. OtheFurther, some studies have shown racial disparities even after adjusting for SES. In a meta-analysis of 20 studies representing a total of 14,013 African Americans and 76,111 white American women diagnosed with breast cancer from 1961 to 2003, Newman concluded that African American ethnicity is a significant and independent predictor of poor outcome from breast cancer, even after accounting for SES . Also, aOthers argue against a biologic hypothesis for racial disparities. In a study of breast cancer-specific mortality rates for women in Chicago, New York City, and the United States from 1980–2005, race-specific rate ratios were used to measure the disparity in breast cancer-specific mortality. In all three locations the black and white rates were similar in the 1980s and remained that way until the 1990s, when the white rates started to decline while the black rates remained constant, just as the benefits from early detection by mammography and from treatment were noticeable -62. ThesThe goal of our present study was to assess racial/ethnic disparities within three levels of SES and within the same stage of disease so that variability among treatment and access to care would be minimized. We also adjusted for ER/PR/HER2 because of the known propensity of African American and Hispanic women to have hormone receptor-negative and, in particular, triple-negative phenotype ,19,22,40The present investigation has shown that for women with stage 1 breast cancer, there is no disparity among any race/ethnicity regardless of the SES category. In addition, there is no black/white disparity within the lowest SES category regardless of stage of disease, but a disparity is apparent in the higher SES categories. African Americans in the intermediate and highest SES categories with stages 2 and 3 breast cancer have increased risk of mortality when compared with whites. Interestingly, low SES Hispanic patients with stages 2 and 3 disease have a lower risk of mortality when compared to low SES white patients, similar to what has been described in the "Hispanic Paradox" .As is often the case, a correlational study raises more questions than answers. On the one hand, a differential tumor or host biology does not seem to be plausible because there were no differences in risk of mortality among any race/ethnicity in stage 1 and there was no black/white disparity for women in the lowest SES category regardless of stage. On the other hand, for higher stages of disease, black patients in the same, higher SES category had an increased risk of mortality as compared to white patients while Hispanics in the lowest SES category at higher stages had decreased risk of mortality as did APIs in Stage 3.The findings of this study raise the question of whether tumor or host factors play a role in advanced stages of disease. Do black, white, Hispanic, and API patients respond differentially to treatments? Data regarding racial/ethnic differences in the pharmcogenomics of chemotherapy and endocrine response and toxicities are limited -66. AlteThe results of this population-based registry study cannot definitively answer these perplexing questions, but at least in stage 1 disease, a differential tumor biology appears unlikely. It also appears that SES plays a prominent role in cancer outcomes although genetic, environmental, societal, lifestyle, and health provider factors may also contribute to racial disparities, and they should not be overlooked .The limitations of population-based cancer registry investigations including exclusion of subjects without ER, PR, and HER2 are well known ,45,70-72We recognize that determination of race/ethnicity can be problematic and arbitrary. Hispanic ethnicity may include women from Mexico, Central and South America, Spain, as well as Puerto Rico and Cuba. The category API may include women from Asia, the Indian Continent, and the Pacific Islands. We also recognize that our measure of SES was at the neighborhood level rather than at the individual level. The CCR does not obtain the information necessary to determine individual SES but others have commented on the usefulness of composite SES measures ,79 In adLastly, other than age, we have no information about reproductive history and lifestyle risk factors such as nulliparity, multiparity, breast feeding, diet, body fat distribution, use of alcohol, oral contraceptives, or hormone replacement treatments that may determine the type of breast cancer and ultimately impact survival, -88.Despite these shortcomings, our study is unique because of the large number of cases reported to the statewide cancer registry from an ethnically diverse population. Unlike other studies that employed different methodologies of SES  or had eOur research has shown that when breast cancer-specific mortality is analyzed either by race/ethnicity or by SES, significant differences exist among the races with respect to age at presentation, stage at diagnosis, ER/PR/HER2 subtype, and tumor grade. However, when adjusting analyses for these variables and comparing cases within stage and SES strata, much of the black/white disparity disappears.SES plays a prominent role in breast cancer-specific mortality but it does not fully explain the racial/ethnic disparities and continued research in genetic, societal, and lifestyle factors is warranted.The authors declare that they have no competing interests.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/449/prepub


To investigate the prevalence rate of cigarette smoking and its socio-demographic and clinical correlates in Chinese schizophrenia inpatients receiving antipsychotic mono-therapy.This study was a cross-sectional, two-site, hospital-based survey. Four hundred and twenty-nine schizophrenia patients  were consecutively recruited from psychosis inpatient wards of two large specialty psychiatric hospitals in mainland China. Patients were assessed using a cigarette smoking questionnaire, the Positive and Negative Symptom Scale, the Simpson Angus Scale, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale. Socio-demographic and other clinical data were also collected. We calculated the prevalence of current smoking in our sample as well as its indirectly standardized prevalence ratio (ISPR) using data from the 2010 Global Adult Tobacco Survey in China.The prevalence rate of current smoking was 40.6% in our sample, and 57.5% in males and 6.3% in females. The ISPRs of all patients, men and women were 1.11(95%CI: 0.95∼1.29), 1.07(95%CI = 0.91∼1.24) and 4.64(95%CI = 2.12∼8.82), respectively. The overall and male-specific prevalence of current smoking did not differ significantly between patients and the general population. In multiple logistic regression analysis, male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking.Male Chinese inpatients with schizophrenia who received a mono-therapy of antipsychotics were not more likely to smoke than the general population. Cigarette smoking is more common in schizophrenia patients with more severe illness. It has been recognized for many years that there is a much higher prevalence of smoking in schizophrenia patients than in the general population or patients with other mental disorders Although cultural context contribute to cigarette smoking The underlying causal mechanisms of high frequency of smoking in schizophrenia patients are unclear, especially whether smoking is a risk indicator for the development of the illness, a marker of a more severe illness, or an attempt at self-medication Previous studies on the clinical features of smoking schizophrenia patients also yielded inconsistent findings. Some found that smoking was significantly correlated with younger age, earlier age at onset (AAO) of illness, increased number of hospitalizations, elevated risk of suicide, higher doses of antipsychotic agents, more antipsychotic drug induced side-effects, and more severe psychotic symptoms Schizophrenia and related psychotic syndromes can be understood as disorders of adaptation to social contextThe study protocol was approved by the Ethic Committees of Wuhan Mental Health Center and Shenzhen Kangning Hospital. Before respondents were interviewed, written consent was obtained from all of the subjects and their guardians, and declarations of anonymity and confidentiality had been made. Verbal consent also obtained from each included inpatient's responsible physician. For the compensation of time spent in participating in this study, each respondent had been given a gift prior to the interview.This cross-sectional, two-site, hospital-based survey was conducted between January 2011 and June 2013. Subjects were recruited by consecutively screening patients with schizophrenia who attended the psychosis inpatient wards of Wuhan Mental Health Center and Shenzhen Kangning Hospital in Wuhan and Shenzhen, two of the largest cities in China. These two cities, one located in south-central area and the other located in southeastern coastal area of China, are typical examples of the metropolitan regions of mainland China, in terms of their financial conditions and levels of health care service. Both hospitals are the largest specialty psychiatric hospitals of local areas, with 610 and 450 hospital beds, respectively. They are responsible for mental health services of the residents of Wuhan and Shenzhen, and thus have a catchments area of approximately 10,020,000 and 10,547,400, respectively.Patients who satisfied the following inclusion criteria were invited to participate in the study: 1) age 18–60 years; 2) men and women with a DSM-IV diagnosis of schizophrenia; 3) inpatients of psychosis wards; 4) had been treated with a stable dose of oral antipsychotic mono-therapy for at least four weeks before entry into the study, irrespective of the presence or absence of combination use of other non-antipsychotic drugs. Subjects with severe medical conditions, obvious intellectual disorders, active non-nicotine substance dependence, and organic psychosis, and who were prescribed two or more classes of antipsychotic agents, were excluded from this study. Although our subjects were inpatients, they were allowed to smoke regularly every day, except the time for sleep and taking drugs. Patients could easily buy cigarettes of most cigarette brands at reasonable prices in their psychiatric wards.The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of antipsychotic drugs were recorded using a standardized protocol and data collection procedure. Data on patients' socio-demographic variables and clinical characteristics were collected through a questionnaire designed for this study. AAO refers to age at the first psychotic symptom reported by the patients themselves or informants We also administered a standardized cigarette smoking questionnaire to record smoking habit of each subject, including the average number of cigarettes smoked per day. Items of smoking questionnaire were adapted from the instruments of 2008 US National Health Interview Survey (hereafter refer to “NHIS definition” of smoking) Psychopathology of schizophrenia in the 4-week period preceding the interview was measured using the Chinese version of Positive and Negative Symptom Scale (PANSS) with subscales for positive symptoms (PANSS-P), negative symptoms (PANSS-N), and general psychopathological symptoms (PANSS-G) Two raters, an experienced psychiatrist and a clinical psychologist, were responsible for all of the assessments. Prior to the study, both raters underwent a training course on the use of PANSS, SAS, BARS, and AIMS. Before the beginning of this study, an inter-rater correlation coefficients ranging from 0.81 to 0.93 was obtained in 11 voluntary schizophrenia patients between the two raters for all assessment scales.Once participants agreed to participate in this study, they were told that the main goal of this study was to help clinicians understand the relationship between schizophrenia and smoking, and the results might be helpful for the management and rehabilitation of schizophrenia. Hence, supplying real information about the smoking behaviors was of vitally importance for this study. Our raters were also required to be patient to help respondents recall their smoking details during the course of interview. The completeness of all interview and physical examination records was checked daily by the survey team leader. Errors, omissions and other flaws were solved during the fieldwork period of this survey.For the analysis, we used the SPSS software for Windows, version 15.0 (SPSS Ltd.). According to the smoking status diagnosed by NHIS definition, prevalence rates for ever, current and former cigarette smoking were calculated. Because the number of former smoker in our sample was very small (N = 3), the following univariate and multivariate analyses only focused on current and never smokers. In univariate analysis, the comparison between current smokers and never smokers with respect to socio-demographic and clinical characteristics was performed by independent sample t-test, Mann-Whitney U test, and chi-square test as appropriate. Multivariate logistic regression was used to identify factors associated with current smoking. Associations between current smoking and all potential predictors were assessed in univariate analyses, followed by multivariate analyses of the selected subsets. A variable was selected if it was statistically significant at the nominal two-sided 0.05 level in univariate analysis. We quantified associations of predictors and current smoking by calculating odds ratios (ORs) with 95% confidence intervals (CIs) for each variable.To clarify whether schizophrenia inpatients have higher current smoking rate than Chinese general population, we introduced the latest smoking data from the 2010 Global Adult Tobacco Survey in China (2010 GATS China) Out of 976 schizophrenia inpatients who were screened during the study period, 617 were on antipsychotic mono-therapy treatment and fulfilled the inclusion criteria. Among them, 56 refused, 93 did not complete assessment, and 39 were ineligible for other reasons, leaving 429 (69.5%) patients completed the interview and physical examination. The mean age at the time of this survey was 33.1 years , and 66.9% of the subjects were male. The numbers of patients using promethazine, perphenazine, chlorpromazine, sulpiride, paliperidone, clozapine, risperidone, quetiapine, olanzapine, amisulpride, and aripiprazole were 2, 19, 76, 5, 1, 117, 95, 24, 53, 2, and 35, respectively. Therefore, for the antipsychotics used, the second-generation antipsychotic (SGA) mono-therapy was used more often compared to the first-generation antipsychotic (FGA) (77.4% vs. 22.6%) mono-therapy. Other socio-demographic and clinical characteristics of the schizophrenia inpatients are displayed in the first three columns of Of the 429 patients, 177 (41.3%) were identified as ever smokers, 3 as former smokers (0.7%) and 174 as current smokers (40.6%); 57.5% of male (N = 165) and 6.3% of female patients (N = 9) were current smokers. Among the current smokers, the mean number of cigarettes consumed per day was 16.1 , while 15.2% of them smoked ≤ 9 cigarettes daily, 43.5% of them smoked 10–19 cigarettes, and 41.4% smoked ≥ 20 cigarettes (heavy smoking). For current smokers, the mean age at regular smoking onset was 20.6 (SD = 4.6) years, and the mean AAO for schizophrenia was 24.9 (SD = 7.4) years, with 75.8% starting regular smoking before the onset of schizophrenia. The age of regular smoking start in patients was significantly earlier than their age of illness onset .The ISPRs of all patients, male and female patients were 1.11(95%CI: 0.95∼1.29), 1.07 (95%CI: 0.91∼1.24) and 4.64(95%CI: 2.12∼8.82), respectively . These rThe socio-demographic and clinical characteristics of current and never smokers are shown in the fourth to seventh columns of This study demonstrated that the prevalence of current smoking was 40.6% and the ISPR was 1.11 in Chinese schizophrenia inpatients currently receiving a mono-therapy of antipsychotics. However, both the overall and male-specific prevalence rates of current smoking did not differ significantly between patients and the general population. Only female Chinese inpatients with schizophrenia seem to have higher smoking risk than the general population, but the absolute difference  between the two prevalence rates is really too small. Considering the finding that the female-specific prevalence (6.3%) was too low, and the comparable prevalence between the whole sample and the general population, it is difficult to conclude that Chinese inpatients with schizophrenia are more likely to smoke than the general population. This study further demonstrated that current smokers of patients had significantly lower rate of heavy smoking than those of the general population, indicating that Chinese schizophrenia smokers are not heavy cigarette smokers. Although we found the majority of smokers (75.8%) started regular smoking before the disease onset, the mean age of starting to smoke (20.6 years) was similar to that of the general population; these phenomena might not support the viewpoint that schizophrenia patients start regular smoking in greater numbers during adolescence than the normal population in Western countries In addition to showing the differences in smoking characteristics between individuals with schizophrenia and the general population, our study also found lower current smoking prevalence, including gender-specific and overall prevalence, of schizophrenia inpatients than those reported previously in Western studies [US  When we study the association between smoking and schizophrenia, as measured by OR, it is noteworthy that the estimated ORs have close relationship with the smoking prevalence rates of the general population, because the conclusions regarding whether patients have higher, lower or comparable risk of smoking, highly depending on the control population used. For example, two studies conducted in Turkey and US reported similar smoking rates in their schizophrenia sample (50% and 51%) Analyses of correlates of current smoking revealed that, in schizophrenia inpatients, smoking was more prevalent among patients who were male, were older, were in poor marital status, used alcohol, took FGAs, had longer illness duration, had multiple hospitalizations, and had more severe negative symptoms. These findings indicate that the potential etiologies of smoking in schizophrenia are complex and multifactorial. In this study, male sex, older age (below 60 years old), and unmarried status were identified as significantly risk factors for smoking, these findings are in line with previous reports for both the general population It has been suggested that individuals with schizophrenia use tobacco to gain relief from EPS induced by antipsychotic medication. Cigarette smoking increases the activity of hepatic CYP 1A2 enzymes, thus decreasing the concentration of antipsychotic drugs After adjusting confounders, smoking was still associated with more hospital admissions and longer illness duration; both findings indicated that our smoking cases have a more severe disease course. Previous studies also support these findings The strength of this study was ensuring the analysis on the association of smoking with types and doses of antipsychotic agents in subjects receiving neuroleptic mono-therapy treatment, by eliminating the masked effect of patients receiving multiple antipsychotic medications. However, this study has several limitations that should be noted. First, our study sample consists of inpatients on antipsychotic mono-therapy only and can’t represent all patients with schizophrenia. Therefore, the results may not be applicable to outpatients and inpatients on antipsychotic poly-therapy. In addition, our sample was selected from specialty psychiatric hospitals of two large cities in mainland China. Although the prevalence and correlates identified in our study seem consistent with several findings in previous reports, whether they also apply to other institutions of China is still questionable. So the findings from this study should be generalized with caution. Second, our study was a cross-sectional, observational study in nature, thus the cause-consequence relationships between smoking and risk factors could not be created. Third, the definition of smoking used in the present study is broader, because it defines a current smoker as an ever smoker who currently smokes daily or on some days In summary, smoking in Chinese male schizophrenia inpatients, who were receiving antipsychotic mono-therapy, is as prevalent as the general population, and the overall prevalence of smoking in Chinese schizophrenia inpatients is lower than most figures reported in Western literature. Smoking had relationship with gender, age, and marital status; Illness severity-related indicators seemed to have close relationship with smoking in this patient population. Smoking may serve as an important clinical marker of severe illness in individuals with schizophrenia. Given the harmful consequences and its association with more severe illness, effective measures to promote smoking cessation in schizophrenia should be implemented in Chinese patients with schizophrenia.


Male breast cancer, which represents only 1% of all breast cancers, is occasionally associated with a family history of breast cancer. Sporadic male breast cancers presenting with another primary breast cancer are extremely rare. In this article, we report on a 70-year-old male patient with bilateral multifocal and synchronous breast cancer and without a family history of breast cancer. Male breast cancer represents 1% of all breast cancers. It occasionally occurs in patients with a family history of this disease. Synchronous bilateral breast cancer in men is extremely rare. In this report, a 70-year-old male with synchronous bilateral multifocal cancer of the left breast (LB) with no family history of breast cancer is presented.Breast cancer is a rare disease in men. According to international statistics, this pathology represents 1% of all breast neoplasia, whereas in Cuba, it represents 0.8% .Among the factors that predispose its occurrence, we include exposure to ionising radiation, the administration of oestrogens, and diseases related to hyperestroginisation, such as cirrhosis of the liver and Klinefelter syndrome .Genetic factors such as the mutation of the BRCA1-2 genes or kinship are related to the incidence of this disease, although the majority of those affected do not present risk factors , 5.Unlike its incidence in women, who have a bimodal age–frequency distribution, its incidence in men is unimodal, with a peak incidence at 71 years. It has a central, sub-areolar location, and nearly 85% of cases show up in a physical exam. The most common histological type is invasive (infiltrating) ductal carcinoma with an incidence of 85–90% –8.Although the disease presents similarities in both genders, its rarity and the small number of cases do not allow the carrying out of clinical research necessary to develop optimum treatment. This is why treatment is based on empirical advances made in breast cancer in women .In this report, we present a 70-year-old man with bilateral breast cancer, apparently synchronous, multifocal, and with differing histologies in the LB, with no family history of breast cancer. In this case, the clinical criteria for hereditary familial cancer are evaluated .–Cancer at less than or equal to 40 years.–Diagnosis of breast and ovarian cancer in the same individual.–Two or more cases, one of which is less than 50 years old or bilateral.–A case of breast cancer, less than or equal to 50 years and a case of ovarian cancer in a first- or second-degree relative.–Three cases of breast and ovarian cancer in first- and second-degree relatives.–Male breast cancer and breast or ovarian cancer in first- or second-degree relatives.High risk–Two first-degree relatives if both have been diagnosed between the ages of 51 and 60.–A first- and second-degree relative , if the sum of their ages is less than or equal to 118 years.Moderate riskThis is a 70-year-old white male with a history of type II diabetes mellitus. The patient denied any family history of breast or any other type of cancer. This information comes from a genetic and breast cancer consultation, in which the family history, physical examination, and mammography were carried out on the first-degree relatives of the patient. The patient came to the Oncology Institute complaining of lumps in both breasts for the past two months.Upon physical examination, a hard lump, measuring 30 x 20 mm, was felt in the right breast (RB) and armpit, with an irregular surface, poorly defined edges, mobile, with fixation and retraction of the nipple–areolar complex accompanied by hard, mobile, and ipsilateral adenopathy. The LB presented a hard, irregular lump, measuring 20 x 25 mm, with poorly defined edges in the retroareolar region with hard, mobile, and ipsilateral adenopathy .On performing the breast ultrasound, a solid, irregular lump was observed in RB, measuring 30 x 25 mm, of heterogeneous texture, with microcalcifications in its interior and adenopathies with a pathological appearance, while in the LB, a solid lump was observed, with a heterogeneous texture, measuring 22 x 20 mm, with irregular contours, located in the retroareolar region with no evidence of pathological adenopathies. The bilateral mammogram revealed the presence of a lump in the RB, with diffuse edges, infiltrates, measuring 40 x 35 mm, producing retraction and flattening of the nipple, with pathological microcalcifications in its interior, the spikes of the lump were close to the pectoralis major muscle, while in the LB, a lump was observed measuring 25 x 20 mm with diffuse spiked edges, with pathological microcalcifications both within and outside it . Both teA freeze biopsy was performed, and invasive papillary carcinoma was reported for both breasts. A bilateral modified radical mastectomy was carried out.The histopathological examination revealed the presence of invasive ductal carcinoma in the RB, nuclear grade (NG) II, Bloms Richardson (BR) II, RE 45%, RP 85%, HER-2 +1, KI 67 40% with vascular and lymphatic invasion, and a tumour size of 45 x 40 x 30 mm. There were 11 positive nodes of a total of 20 analysed (11 of 20). In the LB, two  lumps are reported, the larger measuring 23 x 20 x 15 mm corresponding to invasive ductal carcinoma, NG II, BR-II, RE 90%, RP 90%, HER-2 +1, KI 67 20%, with papillary areas, infiltration of adipose tissue, neural invasion, and vascular and lymphatic permeation. The other lump corresponds to invasive papillary carcinoma, measuring 25 x 15 x 15 mm and presented multiple calcifications. The lymph nodes examined showed two positive lymph nodes (2 of 18) –5. The cAccording to the pTNM classification, this corresponds to pT2N3M0, stage IIIC for RB and pT2N1M0, stage IIB for LB. The patient was assessed in a multidisciplinary consultation where chemotherapy treatment was decided upon: four cycles of Adriamycin/Cyclophosphamide and four cycles of Taxol, in addition to radiation therapy to both surgical beds and supraclavicular fossa, followed by hormone therapy (one tablet of Tamoxifen daily for five years). At the present time, the patient’s condition is under control, and he is in follow-up with mastology.Breast cancer in men is a rare pathology. The median age at diagnosis is 60–70 years, although it can affect men of all ages. A bilateral, synchronous presentation is extremely rare, with an incidence of 1–2.5% of the total number of patients with breast cancer –13.Bilateral breast cancer is defined as the presence of an independent primary malignant tumour in each mammary gland; while the term ‘synchronous’ refers to the presence of primary tumours in both breasts, which are diagnosed simultaneously. According to McCredie, this term also includes the diagnosis of contralateral tumours that occur within the first six months following diagnosis of the primary tumour, and according to Heron, within the first year of the initial diagnosis , 15, 16.in situ has a frequency of 10% and is mostly papillary (74%) with a normally cystic presentation. Invasive papillary carcinoma is twice as frequent in men as it is in women (2–4% versus 1%) [The most frequent histological type in men is the invasive ductal carcinoma (85–90%). Other rarer invasive tumours are invasive (4.5%) and mucinous (2.8%) papillary carcinoma. Carcinoma rsus 1%) , 18.With respect to the involvement of the lymph nodes in breast carcinoma in men, it has been observed that the more advanced the average age at diagnosis, the more likely that there will be lymph node involvement presenting at a more advanced stage .In males, these tumours show a large oestrogen receptor (80–90%) and progesterone receptor (73–81%) expression, even higher than in women . Some studies have shown a lower HER-2 expression in men (2–15%) than in women 18–20%), although the data are inconsistent , 20.%, althouDue to the rarity of the disease, there are no controlled prospective studies that support a specific therapeutic management strategy. Therefore, almost all the management strategies in men are the result of retrospective studies of a series of cases and experience with women. The mainstay of treatment is based on the local and regional control of the disease with surgery and radiation therapy and in systemic control with hormone therapy and chemotherapy .In the case of our patient, the histological types found correspond to those reported in the literature as the most frequent: papillary and invasive (infiltrating) ductal carcinoma, with multifocality with different histological types being truly rare . The resWe are dealing with an uncommon presentation of breast cancer in men: synchronous, bilateral, and multifocal with different histological types in the LB, with no family history of the pathology, or related risk factors, which is why its publication is considered important.