Altered hormone expression induced genetic changes leads to breast cancer.

PURPOSE OF REVIEW: Breast cancer ranks first among gynecological cancer in India. It is associated with urbanization, changes in lifestyle and obesity. Hormones also play a crucial role in the development of breast cancer. Steroid hormones play critical role in development of breast cancer. RECENT FINDING: Breast cancer is caused due to alteration in different hormone expressions leading to genetic instability. Loss or gains of functions due to genetic instability were associated with the alterations in housekeeping genes. Up-regulation in c-myc, signal transducer and activator of transcription (STAT), CREB-regulated transcription coactivator (CRTC), and eukaryotic translation initiation factor 4E (eIF4E) may cause the development of breast cancer. Peptide hormones are commonly following the phosphoinositide 3-kinases (PI3K) pathway for activation of cell cycle causing uncontrolled proliferation. Although steroid hormones are following the Ras/Raf/mitogen-activated protein kinase (MEK) pathway, their hyper-activation of these pathways causes extracellular-signal-regulated kinase (ERK) and MAPK activation, leading to carcinogenesis. SUMMARY: Alteration in cell cycle proteins, oncogenes, tumor suppressor genes, transcription and translation factors lead to breast cancer. Apoptosis plays a vital role in the elimination of abnormal cells but failure in any of these apoptotic pathways may cause tumorigenesis. Hence, a complex interplay of hormonal and genetic factors is required to maintain homeostasis in breast cells. Imbalance in homeostasis of these hormone and genes may lead to breast cancer.

Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

Impact of HPV strains on molecular mechanisms of cervix cancer.

PURPOSE: Cervical cancer accounts for a high number of deaths worldwide. Risk factors are extensive for cervix cancer but Human papillomavirus (HPV) plays a prime role in its development. Different strains of HPV are prevalent globally, which show different grades of mortality and morbidity among women. This study is planned to evaluate the molecular mechanism of different strains of HPV infection and progression leading to cervix cancer. METHODS: This review includes different research articles on cervix cancer progression reported from India and all over the world. RESULTS: HPV 16 and 18 are prevalent strains using heparan sulfate-independent and dependent pathways for viral replication inside the cell. It also uses transcription mechanisms through NF-kappa B, FOXA-1, and AP-1 genes while strains like HPV-35, 45, and 52 are also predominant in India, which showed a very slow mechanism of progression due to which mortality rate is low after their infection with these strains. CONCLUSION: HPV uses E6 and E7 proteins which activate NF-kappa B and AP-1 pathway which suppresses the tumor suppressor gene and activates cytokine production, causing inflammation and leading to a decrease in apoptosis due to Caspase-3 activation. In contrast, the E7 protein involves HOXA genes and decreases apoptotic factors due to which mortality and incidence rates are low in viruses that use E7 motifs. Some HPV strains employ the cap-dependent pathway, which is also associated with lower mortality and infection rates.

COVID-19-associated 2020 lockdown: a study on atmospheric black carbon fall impact on human health.

The mean mass concentrations of black carbon (BC), biomass burning (BC)bb, and fossil fuel combustion (BC)ff have been estimated during March-May 2020 (during the COVID-19 outbreak) and March-May 2019 at a semiarid region of Agra over the Indo-Gangetic basin region. The daily mean mass concentration of BC in 2020 and 2019 was 3.9 and 6.9 µg m-3, respectively. The high monthly mean mass concentration of BC was found to be 4.7, 3.4 and 3.3 µg m-3 in Mar-2020, Apr-2020, and May-2020, respectively, whereas in Mar-2019, Apr-2019, and May-2019 was 7.7, 7.5 and 5.4 µg m-3, respectively. The absorption coefficient (babs) and absorption angstrom exponent (AAE) of black carbon were calculated. The highest mean AAE was 1.6 in the year 2020 (Mar-May 2020) indicating the dominance of biomass burning. The mean mass concentration of fossil fuel (BC)ff and biomass burning (BC)bb is 3.4 and 0.51 µg m-3, respectively, in 2020 whereas 6.4 and 0.73 µg m-3, respectively, in 2019. The mean fraction contribution of BC with fossil fuel (BC)ff was 82.1 ± 13.5% and biomass burning (BC)bb was 17.9 ± 4.3% in 2020, while in 2019, fossil fuel (BC)ff was 86.7 ± 13.5% and biomass burning (BC)bb was 13.3 ± 6.7%. The population-weighted mean concentration of BC, fossil fuel (BC)ff, and biomass burning (BC)bb has been calculated. The health risk assessment of BC has been analyzed in the form of attributable relative risk factors and attributed relative risk during the COVID-19 outbreak using AirQ + v.2.0 model. The attributable relative risk factors of BC were 20.6% in 2020 and 29.4% in 2019. The mean attributed relative risk per 10,000,000 populations at 95% confidence interval (CI) due to BC was 184.06 (142.6-225.2) in 2020 and 609.06 (418.3-714.6) in 2019. The low attributed factor and attributed relative risk in 2020 may be attributed to improvements in air quality and a fall in the emission of BC. In 2020, due to the COVID-19 pandemic, the whole country faced the biggest lockdown, ban of the transportation of private vehicles, trains, aircraft, and construction activities, and shut down of the industry leading to a fall in the impact of BC on human health. Overall, this was like a blessing in disguise. This study will help in future planning of mitigation and emission control of air pollutants in large and BC in particular. It only needs a multipronged approach. This study may be like torch bearing to set path for mitigation of impacts of air pollution and improvement of air quality.

Anthropogenic aerosols in precipitation over the Indo-Gangetic basin.

This study investigated the concentration of heavy metals in rainwater (RW) at a semi-arid region of the Indo-Gangetic basin to understand the influence of local, regional, or long-range transport of air pollutants during the monsoon and non-monsoonal rain. The concentration of heavy metals in RW was determined using Atomic Absorption Spectrophotometer with Graphite Furnace, the scavenging ratio was estimated, and source interpretation was carried out using Principle Component Analysis (PCA) and HYSPLIT model. Ca was the highest contributor in RW followed by Na, Fe, Mg, and Al whereas Ba, Cr, Cu, Mn, Ni, Pb, and Zn were found in trace quantity. During the non-monsoon period, the crustal component (Ca) was the highest; however, during the monsoon, sea salt components (Na and Fe) were found higher. The scavenging ratio for metals was estimated and was found many times higher than those reported over European sites. The moderate concentration of heavy metal in RW was found with higher wind from South (S), South-West (SW), and North-West (NW) directions. Air mass back trajectory shows a significant contribution of metals from the Arabian Sea (South-Westerly wind) during active monsoon, whereas, in the non-monsoon season, the air masses mainly originated from the north-west indicating a contribution from wind-blown dust. The correlation analysis has shown the positive correlations between Ca and Mg, Mg and Na, Na and Cu, Al and Zn, Zn and Ba, Ba and Cr, and Cr and Zn. Principal Component Analysis (PCA) indicated loading of Ca, Na, Mg, Cu, Mn, and Ni in the first factor suggesting their crustal origin, whereas the second factor showed high loading of Al, Ba, Zn, Cr, and Ni indicating vehicular exhaust and industrial emission as their major sources, and loading for Ba and Mg in the third factor indicates the mixed contribution from both natural and anthropogenic sources in rainwater during the monsoon and non-monsoon periods. The data of this study can be used in the air pollution transport model. This study will help in source interpretation over the Indo-Gangetic basin and will help in planning for National Clean Air Program (NCAP) and deriving critical load.

Adsorptive removal of oxytetracycline using MnO2-engineered pine-cone biochar: thermodynamic and kinetic investigation and process optimization.

Indiscriminate use of oxytetracycline is linked to the development of antibiotic-resistant genes, posing a serious threat to human health and ecosystem balance. This article reports the adsorptive elimination of oxytetracycline (OTC) from aqueous solution using a newly developed MnO2-modified pine-cone biochar (MnO2/PCBC). The MnO2/PCBC was characterized using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, CHNS analyzer, inductively coupled plasma-optical emission spectroscopy, and Brunauer-Emmett-Teller N2 adsorption analyzer. Batch adsorption experiments, designed using the central composite design framework of response surface methodology, were conducted to investigate the influence of process variables on the adsorption of OTC onto MnO2/PCBC. The optimized conditions for achieving maximum removal (88.1%) were found to be at pH 8, MnO2/PCBC dose 0.44 g/L, initial OTC concentration 200 mg/L, and temperature 303 K. The adsorption process follows Langmuir (R2=0.95) and Freundlich (R2=0.95) isotherms and pseudo-second-order (R2=0.99) adsorption kinetics. The adsorption process was found to be endothermic (ΔH0 = 33.04 kJ/mol) and spontaneous in nature (ΔG0 from -1.33 kJ/mol at 283 K to -5.65 kJ/mol at 313 K). The synthesized MnO2/PCBC could be recycled and reused for OTC removal with a percentage removal of around 80% after fifth cycle. The results indicate an effective removal of oxytetracycline with only 0.44 g/L MnO2/PCBC with maximum adsorption capacity of 357.14 mg/g which demonstrates improved performance in comparison to many adsorbents reported in literature. This implies that MnO2/PCBC offers potential to be developed into a cost-effective technique for antibiotic removal from water.

Combined Interaction of Cellular and Extracellular Components Causes Genetic Cascade Activation in Breast Cancer Metastasis.

Breast cancer (BC) consists of malignant cells as well as surrounding nonmalignant cells - fibroblasts, macrophages, endothelial cells, lymphocytes, neutrophils, mesenchymal stem cells, and extracellular matrix (ECM). This surrounding stroma is referred to as the breast tumor microenvironment (BTME). The components of BTME interact with cancerous breast cells for the promotion of BC. The reciprocal cross talk between BTME and neoplastic breast cells, through the secretion of chemicals, growth factors, and chemokines, may lead to cell proliferation, migration, metastasis as well as immune response suppression. Multiple genetic loci, in association with stromal components, are linked to immunological stimuli to induce BC in ductal cells. These genes participate in tumor activation pathways and promote carcinogenesis via fibroblast, leukocyte, and endothelial-cell-mediated responses. The collaborative effect of the cellular components and BTME-associated genes plays vital role in tumor initiation and metastasis of breast cells. This process involves genes which cause degenerative changes in ECM leading to epithelial-mesenchymal transitions, which finally causes metastatic BC. This shows that metastatic BC results from combined activation of different cellular and extracellular components, and their activity is primarily controlled by activation of the genetic cascade. These components work simultaneously to cause metastatic BC.

Assessment of hypertension association with arsenic exposure from food and drinking water in Bihar, India.

Epidemiological studies have associated chronic exposure to arsenic (As) from drinking water with increased risk of hypertension. However, evidence of an association between As exposure from food and hypertension risks is sparse. To quantify the association between daily As intake from both food (rice, wheat and potatoes) and drinking water (Aswater) along with total exposure (Astotal) and hypertension risks in a study population in Bihar, India, we conducted an individual level cross-sectional analysis between 2017 and 2019 involving 150 participants. Arsenic intake variables and three indicators of hypertension risks (general hypertension, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) were derived, and any relationship was quantified using a series of crude and multivariable log-linear or logistic regression models. The prevalence of general hypertension was 40% for the studied population. The median level of HDL was 45 mg/dL while median value of LDL was 114 mg/dL. Apart from a marginally significant positive relationship between As intake from rice and the changes of LDL (p-value = 0.032), no significant positive association between As intake and hypertension risks could be ascertained. In fact, Astotal was found to be associated with lower risks of general hypertension and higher levels of HDL (p-value = 0.020 and 0.010 respectively) whilst general hypertension was marginally associated with lower Aswater (p-value = 0.043). Due to limitations regarding study design and residual confounding, all observed marginal associations should be treated with caution.

Human papillomavirus sequencing reveals its usefulness for the management of HIV-infected women at risk for developing cervical cancer.

AIM: Next-generation sequencing (NGS) is able to describe the composition of human papillomaviruses (HPVs) as percent (%) reads rather than positive/negative results. Therefore, we used this unique approach to assess the prevalence of cervical HPVs of HIV infected (HIV+) in order to understand the determinants of being infected with higher % reads of high risk (HR)-HPVs and cervical abnormalities of atypical squamous cells of unknown significance or higher (ASCUS+). METHODS: Study included 66 women characterized for relevant risk factors/cytology. Receiver-operating curve curve was used to derive the optimal % read cut point to identify ASCUS+ in relation to any HR-HPV genotype or other specific HPV genotypes. The determinants of ASCUS+ and HR-HPVs were tested using logistic regression. RESULTS: Women with >20% reads of any HR-HPV or >12% any HR-HPV other than HPV 16/18 were 5.7 and 12.6 times more likely to be diagnosed with ASCUS+, respectively. Lower CD4 count was a significant determinant of >20% reads of HR-HPV (odds ratio [OR] = 4.1) or >12% any HR-HPV other than HPV 16/18 (OR = 4.5). CONCLUSION: We envision that the NGS-based HPV detection will be more accurate for screening and management of HIV+ at risk for developing cervical cancer (CC). We raise concerns regarding the limitations of 16/18-based HPV testing for triage and the efficacy of current HPV vaccines for preventing CC in HIV+.

Rapid Electrochemical Monitoring of Bacterial Respiration for Gram-Positive and Gram-Negative Microbes: Potential Application in Antimicrobial Susceptibility Testing.

Antimicrobial resistance is a grave threat to human life. Currently used time-consuming antibiotic susceptibility test (AST) methods limit physicians in selecting proper antibiotics. Hence, we developed a rapid AST using electroanalysis with a 15 min assay time, called EAST, which is live-monitored by time-lapse microscopy video. The present work reports systematical electrochemical analysis and standardization of protocol for EAST measurement. The proposed EAST is successfully applied for Gram-positive Bacillus subtilis and Gram-negative Escherichia coli as model organisms to monitor bacterial concentration, decay kinetics in the presence of various antibiotics (ciprofloxacin, cefixime, and amoxycillin), drug efficacy, and IC50. Bacterial decay kinetics in the presence of antibiotics were validated by the colony counting method, field emission scanning electron microscopy, and atomic force microscopy image analysis. The EAST predicts the antibiotic susceptibility of bacteria within 15 min, which is a significant advantage over existing techniques that consume hours to days. The EAST was explored further by using bacteria-friendly l-lysine-functionalized cerium oxide nanoparticle coated indium tin oxide as a working electrode to observe the enhanced electron-transfer rate in the EAST. The results are very significant for future miniaturization and automation. The proposed EAST has huge potential in the development of a rapid AST device for applications in the clinical and pharmaceutical industries.

Exposure to respirable and fine dust particle over North-Central India: chemical characterization, source interpretation, and health risk analysis.

This study enhances the understanding of the particulate matters (PM2.5 and PM10) and their physical and chemical behavior over the Taj Mahal, Agra, in North-Central India. The mass concentration was determined, and the shape and size of the particles and chemical characterizations have been carried out using SEM-EDX. The high level and significant variation of PM10 (162.2 µg m-3) and PM2.5 (83.9 µg m-3) were observed. The exceedance factor of the present study region is in critical and moderate condition. Morphological characterization reveals the particles of different shapes and sizes, while elemental analysis shows the presence of Si, Al, Fe, Ca, K, Cl, Mg, Na, Cu, and Zn. The dominance of Si indicated the contribution of natural sources, i.e., soil over this region. Three significant sources, viz. soil/road paved dust/vegetative emissions, vehicular/industrial emissions, and intermingling of dust and combustion particles, have been identified using principal component analysis over North-Central India. Health risk analysis of particulate matter identified carcinogenic and non-carcinogenic metals in the present study, which comes in contact with human beings during inhalation. The non-carcinogenic risk was much higher than the acceptable level. The high carcinogenic risks were found in Zn in PM10 and Cu in PM2.5 for both children and adults.

In Silico and Experimental Evaluation of Primer Sets for Species-Level Resolution of the Vaginal Microbiota Using 16S Ribosomal RNA Gene Sequencing.

Background: Identification of bacteria in human vaginal specimens is commonly performed using 16S ribosomal RNA (rRNA) gene sequences. However, studies utilize different 16S primer sets, sequence databases, and parameters for sample and database clustering. Our goal was to assess the ability of these methods to detect common species of vaginal bacteria. Methods: We performed an in silico analysis of 16S rRNA gene primer sets, targeting different hypervariable regions. Using vaginal samples from women with bacterial vaginosis, we sequenced 16S genes using the V1-V3, V3-V4, and V4 primer sets. For analysis, we used an extended Greengenes database including 16S gene sequences from vaginal bacteria not already present. We compared results with those obtained using the SILVA 16S database. Using multiple database and sample clustering parameters, each primer set's ability to detect common vaginal bacteria at the species level was determined. We also compared these methods to the use of DADA2 for denoising and clustering of sequence reads. Results: V4 sequence reads clustered at 99% identity and using the 99% clustered, extended Greengenes database provided optimal species-level identification of vaginal bacteria. Conclusions: This study is a first step toward standardizing methods for 16S rRNA gene sequencing and bioinformatics analysis of vaginal microbiome data.

Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis.

Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.

Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia.

The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD predisposed versus those who were BPD resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16S rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants. We also identified metabolites that were differentially enriched in these samples by use of untargeted mass spectrometry and mummichog to identify the metabolic pathways involved. Microbial metagenome analysis identified specific pathways that were less abundant in the functional metagenome of the microbiota of BPD-predisposed infants compared with BPD-resistant infants. The airway metabolome of BPD-predisposed infants was enriched for metabolites involved in fatty acid activation and androgen and estrogen biosynthesis compared with BPD-resistant infants. These findings suggest that in extremely preterm infants the early airway microbiome may alter the metabolome, thereby modifying the risk of BPD. The differential enrichment of sex steroid metabolic pathways supports previous studies suggesting a role for sexual dimorphism in BPD risk. This study also suggests a role for metabolomic and metagenomic profiles to serve as early biomarkers of BPD risk.

Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages.

It is clear that IL-10 plays an essential role in maintaining homeostasis in the gut in response to the microbiome. However, it is unknown whether IL-10 also facilitates immune homeostasis at distal sites. To address this question, we asked whether splenic immune populations were altered in IL-10-deficient (Il10(-/-)) mice in which differences in animal husbandry history were associated with susceptibility to spontaneous enterocolitis that is microbiome dependent. The susceptible mice exhibited a significant increase in splenic macrophages, neutrophils, and marginal zone (MZ) B cells that was inhibited by IL-10 signaling in myeloid, but not B cells. The increase in macrophages was due to increased proliferation that correlated with a subsequent enhancement in MZ B cell differentiation. Cohousing and antibiotic treatment studies suggested that the alteration in immune homeostasis in the spleen was microbiome dependent. The 16S rRNA sequencing revealed that susceptible mice harbored a different microbiome with a significant increase in the abundance of the bacterial genus Helicobacter. The introduction of Helicobacter hepaticus to the gut of nonsusceptible mice was sufficient to drive macrophage expansion and MZ B cell development. Given that myeloid cells and MZ B cells are part of the first line of defense against blood-borne pathogens, their increase following a breach in the gut epithelial barrier would be protective. Thus, IL-10 is an essential gatekeeper that maintains immune homeostasis at distal sites that can become functionally imbalanced upon the introduction of specific pathogenic bacteria to the intestinal track.

Gut microbiota composition associated with alterations in cardiorespiratory fitness and psychosocial outcomes among breast cancer survivors.

PURPOSE: In this proof-of-concept pilot study, our purpose was to determine correlations between gut microbiota composition and alterations in cardiorespiratory fitness and psychosocial outcomes among post-primary treatment breast cancer survivors (BCS). METHODS: Composition of the gut microbiota in BCS (n = 12) was assessed at baseline (M0) and at the end of 3 months (M3) using Illumina MiSeq DNA Sequencing of the 16S rRNA gene. Gut microbiota composition was analyzed using the QIIME bioinformatics software and represented through diversity metrics and taxa analyses. Cardiorespiratory fitness, fatigue, anxiety, depression, and sleep dysfunction were assessed at M0 and M3 via the submaximal treadmill test, Fatigue Symptom Inventory, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index, respectively. RESULTS: Increased fatigue interference in BCS was associated with increased mean within-sample Shannon diversity (organism richness and evenness) (p = 0.009). Weighted UniFrac analysis (shifts in taxa relative abundance) revealed significant differences in between-sample (beta) diversity for changes in fatigue interference (p = 0.01) and anxiety (p = 0.022), with a trend observed for fatigue intensity and sleep dysfunction (p < 0.1). Unweighted UniFrac analysis (shifts in taxa types) found significant beta diversity differences for cardiorespiratory fitness (p = 0.026). Prior to false discovery correction (FDR), changes in fitness, fatigue, anxiety, and sleep dysfunction were associated with the frequency of certain gut bacteria genera (e.g., Faecalibacterium, Prevotella, Bacteroides) (p < 0.05). CONCLUSIONS: Correlations may exist between alterations in gut microbiota composition and longitudinal changes in cardiorespiratory fitness, fatigue, and anxiety in BCS. Further research examining the role of the microbiota-gut-brain axis in exercise-induced effects on psychosocial outcomes in BCS is warranted.

Surviving Triple Trouble: Synchronous Breast and Cervical Cancer, HIV Infection and Myocardial Infarction.

Breast and cervical cancer are the two most common cancers in female. However, owing to the contrasting risk factors, synchronous breast and cervical cancer has very rarely been reported. However, noncommunicable disease like cardiovascular disease and different infections has tended to make situations complicated because of complex interaction. In recent years, such cases are being seen frequently and their management is challenging. We report such a case of synchronous breast and cervical cancer complicated by HIV infection and myocardial infarction. This highlights the importance of a wide spectrum of clinical knowledge and skill and interdisciplinary coordination.

Response of germ-free mice to colonization with O. formigenes and altered Schaedler flora.

Colonization with Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host/O.formigenes and microbe/O.formigenes interactions, germ-free or altered Schaedler flora (ASF) mice were colonized with O.formigenes Germ-free mice were stably colonized with O.formigenes suggesting O.formigenes does not require other organisms to sustain its survival. Examination of intestinal material indicated no viable O.formigenes in the small intestine, ∼4 × 106 O.formigenes per 100mg contents in the cecum and proximal colon, and ∼0.02% of total cecal O. formigenes cells were tightly associated to the mucosa. O.formigenes did not alter the overall microbial composition of ASF, and ASF did not impact O.formigenes capacity to degrade dietary oxalate in the cecum. 24-hour urine and fecal collections within metabolic cages in semi-rigid isolators demonstrated that introduction of ASF into germ-free mice significantly reduced urinary oxalate excretion. These experiments also showed that mono-colonized O.formigenes mice excrete significantly more urinary calcium compared to germ-free mice, which may be due to degradation of calcium oxalate crystals by O.formigenes and the subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of defined-flora O.formigenes mouse models should improve our understanding of O.formigenes host and microbe interactions. These data support the use of O.formigenes as a probiotic that has limited impact on the composition of the resident microbiota but providing efficient oxalate degrading function. IMPORTANCE: Despite evidence suggesting a lack of O. formigenes colonization is a risk factor for calcium oxalate stone formation, little is known about O. formigenes biology. This study is the first to utilize germ-free mice to examine the response to mono-colonization with O. formigenes and the impact of a defined bacterial cocktail, altered Schaedler flora, on O. formigenes colonization. This study demonstrates that germ-free mice on their regular diet remain mono-colonized with O. formigenes, and suggests that further studies with O. formigenes gnotobiotic mouse models could improve our understanding of O. formigenes biology and host/O. formigenes and microbe/O. formigenes interactions.

Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.

BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. RESULTS: A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%. CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.

Vaginal Microbiota in Pregnancy: Evaluation Based on Vaginal Flora, Birth Outcome, and Race.

OBJECTIVE: This study aims to evaluate vaginal microbiota differences by bacterial vaginosis (BV), birth timing, and race, and to estimate parameters to power future vaginal microbiome studies. METHODS: Previously, vaginal swabs were collected at 21 to 25 weeks (stored at -80°C), and vaginal smears evaluated for BV (Nugent criteria). In a blinded fashion, 40 samples were selected, creating 8 equal-sized groups stratified by race (black/white), BV (present/absent), and birth timing (preterm/term). Samples were thawed, DNA extracted, and prepared. Polymerase chain reaction (PCR) with primers targeting the 16S rDNA V4 region was used to prepare an amplicon library. PCR products were sequenced and analyzed using quantitative insight into microbial ecology; taxonomy was assigned using ribosomal database program classifier (threshold 0.8) against the modified Greengenes database. RESULTS: After quality control, 97,720 sequences (mean) per sample, single-end 250 base-reads, were analyzed. BV samples had greater microbiota diversity (p < 0.05)-with BVAB1, Prevotella, and unclassified genus, Bifidobacteriaceae family (all p < 0.001) more abundant; there was minimal content of Gardnerella or Mobiluncus. Microbiota did not differ by race or birth timing, but there was an association between certain microbial clusters and preterm birth (p = 0.07). To evaluate this difference, 159 patients per group are needed. CONCLUSIONS: There are differences in the vaginal microbiota between patients with and without BV. Larger studies should assess the relationship between microbiota composition and preterm birth.