Breast cancer diagnosis in Inner-City African American and Hispanic women: The importance of early screening.

PURPOSE: To evaluate the diagnosis of breast cancer in inner-city African-American and Hispanic women under age 50 to support the importance of screening in this population. METHODS: This retrospective chart review included women newly diagnosed with breast cancer from 1/1/2015 to 1/1/2019 in a city hospital mainly serving minority patients. Chi-square and Fisher's exact tests were used for analysis. RESULTS: In this cohort of 108 newly diagnosed African-American (63%) and Hispanic (31%) women, 60/108 (56%) presented with a site of palpable concern for diagnostic workup, and the remaining were diagnosed via asymptomatic screening. Women ages 30-49 were significantly more likely to present with a site of palpable concern when compared to women ages 50-69 (68% vs. 44%, p = 0.045). Additionally, women ages 30-49 were more likely to have triple-negative breast cancer (TNBC) than women ages 50-69 (20% vs. 10%, p = 0.222). However, women ages 30-49 were less likely to have prior mammogram than women ages 50-69 (24% vs. 46%, p = 0.062). CONCLUSION: African-American and Hispanic women ages 30-49 were more likely to present with a site of palpable concern and TNBC than those ages 50-69. However, these young minority women ages 30-49 were less likely to have prior screening mammograms when compared to those ages 50-69. Our data highlights the importance of starting screening mammography no later than age 40 in African-American and Hispanic women. In addition, these women should have risk assessment for breast cancer no later than age 30 and be screened appropriately.

Assessment of Treatment Response after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) for Appendiceal Peritoneal Metastases.

Background The aim of this study was to analyse survival and surrogates for oncological response after PIPAC for appendiceal tumours. Methods This retrospective cohort study included consecutive patients with appendiceal peritoneal metastases (PM) treated in experienced PIPAC centers. Primary outcome measure was overall survival (OS) from the date of diagnosis of PM and from the start of PIPAC. Predefined secondary outcome included radiological response (RECIST criteria), repeat laparoscopy and peritoneal cancer index (PCI), histological response assessed by the Peritoneal regression grading system (PRGS) and clinical response. Results Final analysis included 77 consecutive patients (208 PIPAC procedures) from 15 centres. Median OS was 30 months (23.00-46.00) from time of diagnosis and 19 months (13.00-28.00) from start of PIPAC. 35/77 patients (45%) had ≥3 procedures (pp: per protocol). Objective response at PIPAC3 was as follows: RECIST: complete response 4 (11.4%), 11 (31.4%) partial/stable; mean PRGS at PIPAC3: 1.8 ± 0.9. Median PCI: 21 (IQR 18-27) vs. 22 (IQR 17-28) at baseline (p = 0.59); 21 (60%) and 18 (51%) patients were symptomatic at baseline and PIPAC3, respectively (p = 0.873). Median OS in the pp cohort was 22.00 months (19.00-NA) from 1st PIPAC. Conclusion Patients with PM of appendiceal origin had objective treatment response after PIPAC and encouraging survival curves call for further prospective evaluation.

Biological depolymerization of lignin using laccase harvested from the autochthonous fungus Schizophyllum commune employing various production methods and its efficacy in augmenting in vitro digestibility in ruminants.

A laccase-producing hyper performer, Schizophyllum commune, a white-rot fungus, was evaluated for its ability to selectively degrade lignin of diverse crop residues in vitro. Relative analysis of crop residue treatment using laccase obtained from immobilized cells demonstrated degradation of 30-40% in finger millet straw and sorghum stover, 27-32% in paddy straw, 21% in wheat straw, and 26% in maize straw, while 20% lignin degradation was observed when purified and recombinant laccase was used. Further investigations into in vitro dry matter digestibility studies gave promising results recording digestibility of 54-59% in finger millet straw 33-36% in paddy straw and wheat straw, 16% in maize straw for laccase obtained from cell immobilization method, whereas 14% digestibility was observed when purified and recombinant laccase was used. Sorghum stover recorded digestibility of 13-15% across all straws treated with laccase. The results obtained elucidated the positive influence of laccase treatment on lignin degradation and in vitro dry matter digestibility. The present research gave encouraging figures confirming the production of laccase using the cell immobilization method to be an efficient production method commensurate with purified and recombinant laccase under conditions of submerged cultivation, proclaiming a cost-effective, environmentally safe green technology for effectual lignin depolymerization.

Transcriptomic and epigenomic landscapes of Alzheimer's disease evidence mitochondrial-related pathways.

Alzheimers disease (AD) is the main cause of dementia and it is defined by cognitive decline coupled to extracellular deposit of amyloid-beta protein and intracellular hyperphosphorylation of tau protein. Historically, efforts to target such hallmarks have failed in numerous clinical trials. In addition to these hallmark-targeted approaches, several clinical trials focus on other AD pathological processes, such as inflammation, mitochondrial dysfunction, and oxidative stress. Mitochondria and mitochondrial-related mechanisms have become an attractive target for disease-modifying strategies, as mitochondrial dysfunction prior to clinical onset has been widely described in AD patients and AD animal models. Mitochondrial function relies on both the nuclear and mitochondrial genome. Findings from omics technologies have shed light on AD pathophysiology at different levels (e.g., epigenome, transcriptome and proteome). Most of these studies have focused on the nuclear-encoded components. The first part of this review provides an updated overview of the mechanisms that regulate mitochondrial gene expression and function. The second part of this review focuses on evidence of mitochondrial dysfunction in AD. We have focused on published findings and datasets that study AD. We analyzed published data and provide examples for mitochondrial-related pathways. These pathways are strikingly dysregulated in AD neurons and glia in sex-, cell- and disease stage-specific manners. Analysis of mitochondrial omics data highlights the involvement of mitochondria in AD, providing a rationale for further disease modeling and drug targeting.

Treatment Response After Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastases of Colorectal Originf.

The objective of this study is to analyze oncological outcomes of patients with peritoneal metastases (PM) of colorectal origin treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Background: PIPAC has been demonstrated to be a feasible and safe novel treatment for patients with PM of various origins. Only small series reports on survival after PIPAC by disease entity. Methods: International retrospective cohort study of consecutive patients with PM of colorectal origin. Outcome measures were overall survival (OS), radiological response according to Response Evaluation Criteria in Solid Tumors (RECIST), histological response (peritoneal regression grading score [PRGS]: complete response: 1-4: no response), change of peritoneal cancer index (PCI), and symptom control. Results: Seventeen eligible centers compiled 256 non-selected patients (mean age 61 [50.6-69.2], 43% female) and 606 procedures. Sixty-three percent were treated after 2 lines of chemotherapy, median PCI at PIPAC1 was 18 (interquartile range [IQR] = 10-27). Median OS was 19.00 months (IQR = 12.9-29.8) from diagnosis and 9.4 months (IQR = 4.5-16.8) from PIPAC1. One hundred and four of 256 patients (40.6%) had ≥3 procedures (per protocol [pp]) with the following outcomes at PIPAC3: RECIST: 59.3% partial response/stable, 40.7% progression; mean PRGS: 2.1 ± 0.9. Median PCI was 21 (IQR = 15-29) at baseline and 20 (IQR = 12-27) at PIPAC3 (P = 0.02). Fifty-six (54%) and 48 (46%) patients were symptomatic at baseline and PIPAC3, respectively (P = 0.267). Median OS for the pp cohort was 11.9 months (IQR = 10.7-15.0) from PIPAC1. Independent predictors for survival were radiological response (HR = 3.0; 95% CI = 1.6-5.7) and no symptoms (HR = 4.5, 95% CI = 2.2-9.1) at PIPAC3. Conclusions: Objective treatment response and encouraging survival were demonstrated after PIPAC for colorectal PM. Prospective registry data and comparative studies are now needed in to confirm these data.

Presentation of self-detected breast mass in minority women with limited access to care: Can self-examination assist in early cancer detection?

OBJECTIVE: The United States Preventive Services Task Force recommends against breast self-examination. However, racial disparities exist in mammogram screening. We aimed to evaluate the presentation of women with newly diagnosed breast cancer in the underserved African-American and Hispanic community to provide insight regarding breast cancer screening in this population. METHODS: This retrospective cohort study included women newly diagnosed with breast cancer from 1/1/2016 to 1/1/2018 in an inner city public community hospital. Data was collected via chart review. Patients were divided based on whether they presented with self-detected breast mass. Logistic regression was used for analysis. RESULTS: 59 women were newly diagnosed with breast cancer. 34 women (58%) were African-American, 20 (34%) were Hispanic, and 5 (8%) were other race. Of 59 women, 36 (61%) presented with self-detected breast mass, and only 21 (36%) reported prior mammography. For women who presented with breast mass, the odds of having prior mammography were 78% lower (OR = 0.22, 95% CI 0.07-0.69, p = 0.009), while the odds of having invasive ductal carcinoma were 4.33 times higher (OR = 4.33, 95% CI 1.09-17.25, p = 0.037), as compared to the odds for women not presenting with breast mass. CONCLUSION: Many of our newly diagnosed breast cancer patients were African-American or Hispanic women presenting with self-detected breast mass without prior screening mammography. Further studies should evaluate whether supplemental screening methods, such as breast self-examination or clinical examination, can help with early breast cancer detection in minority women with limited access to care, and such disparities should be considered by organizations when creating screening guidelines.

Immediate effects of Maitland mobilization versus Mulligan Mobilization with Movement in Osteoarthritis knee- A Randomized Crossover trial.

BACKGROUND: Maitland Mobilization or Mulligan Mobilization with Movement (MWM) approaches have been widely used clinically for pain relief and improving mobility in Osteoarthritis knee. However the experimental evidence supporting the usage of these mobilization techniques as sole interventions in management of Osteoarthritis knee is insufficient. OBJECTIVE: To determine from Maitland Mobilization and Mulligan MWM, which mobilization technique will be more effective in reducing pain and improving mobility and function in OA knee immediately after the intervention. STUDY DESIGN: Randomized Crossover trial. MATERIALS AND METHODS: 30 subjects with osteoarthritis knee were recruited and 15 each were randomly allocated to two intervention sequences-one sequence was where Maitland was given first followed by Mulligan and the other was where Mulligan was given first followed by Maitland with a washout period of 48 h in between the two interventions. Numeric Pain Rating Scale (NPRS), Timed Up and Go (TUG) test and Pain free Squat Angle were the outcome measures measured before and immediately after both interventions. RESULTS: Using Repeated Measures ANOVA for analysis of outcomes between and within interventions, no significant differences were seen between Maitland Mobilization and Mulligan MWM, for NPRS, TUG and Pain free Squat Angle (p = 0.18, p = 0.27,p = 0.17) respectively whereas within the interventions both Maitland and Mulligan all outcome measures showed significant changes (p < 0.001). CONCLUSION: Thus it can be seen that Maitland mobilization and Mulligan MWM, both are equally effective in osteoarthritis knee in reducing pain and improving functional mobility and pain free squat angle immediately post treatment.

Digital Morphometrics: A New Upper Airway Phenotyping Paradigm in OSA.

BACKGROUND: OSA is associated with changes in pharyngeal anatomy. The goal of this study was to objectively and reproducibly quantify pharyngeal anatomy by using digital morphometrics based on a laser ruler and to assess differences between subjects with OSA and control subjects and associations with the apnea-hypopnea index (AHI). To the best of our knowledge, this study is the first to use digital morphometrics to quantify intraoral risk factors for OSA. METHODS: Digital photographs were obtained by using an intraoral laser ruler and digital camera in 318 control subjects (mean AHI, 4.2 events/hour) and 542 subjects with OSA (mean AHI, 39.2 events/hour). RESULTS: The digital morphometric paradigm was validated and reproducible over time and camera distances. A larger modified Mallampati score and having a nonvisible airway were associated with a higher AHI, both unadjusted (P < .001) and controlling for age, sex, race, and BMI (P = .015 and P = .018, respectively). Measures of tongue size were larger in subjects with OSA vs control subjects in unadjusted models and controlling for age, sex, and race but nonsignificant controlling for BMI; similar results were observed with AHI severity. Multivariate regression suggests photography-based variables capture independent associations with OSA. CONCLUSIONS: Measures of tongue size, airway visibility, and Mallampati scores were associated with increased OSA risk and severity. This study shows that digital morphometrics is an accurate, high-throughput, and noninvasive technique to identify anatomic OSA risk factors. Morphometrics may also provide a more reproducible and standardized measurement of the Mallampati score. Digital morphometrics represent an efficient and cost-effective method of examining intraoral crowding and tongue size when examining large populations, genetics, or screening for OSA.

Structure of catabolite activator protein with cobalt(II) and sulfate.

The crystal structure of cyclic AMP-catabolite activator protein (CAP) from Escherichia coli containing cobalt(II) chloride and ammonium sulfate is reported at 1.97 Å resolution. Each of the two CAP subunits in the asymmetric unit binds one cobalt(II) ion, in each case coordinated by N-terminal domain residues His19, His21 and Glu96 plus an additional acidic residue contributed via a crystal contact. The three identified N-terminal domain cobalt-binding residues are part of a region of CAP that is important for transcription activation at class II CAP-dependent promoters. Sulfate anions mediate additional crystal lattice contacts and occupy sites corresponding to DNA backbone phosphate positions in CAP-DNA complex structures.

Correlation of seizures and biochemical parameters of oxidative stress in experimentally induced inflammatory rat models.

The role of oxidative stress in the pathogenesis of various conditions including epilepsy, inflammatory bowel disease and rheumatoid arthritis is evolving. The aim of this study was to find out the correlation between various inflammatory models with seizures and antioxidant parameters. Fifty-four male rats were divided into three groups of colitis, adjuvant arthritis and cotton wool granuloma (CWG). Each group had three subgroups of control, model and treatment. Thalidomide was used as treatment in colitis and arthritis group, whereas etoricoxib was used in CWG group. In colitis and arthritis groups, thalidomide was administered for 3 and 17 days, respectively, whereas etoricoxib was administered for 7 days in CWG group. At the end of treatment protocols, a subconvulsive dose of pentylenetetrazole (PTZ) (40 mg/kg i.p.) was injected intraperitoneally to note seizure onset and score. After confirming the presence of inflammation by morphological and histological studies, plasma and brain biochemical parameters of oxidative stress were estimated. The models of colitis, arthritis and CWG were effectively produced as evidenced by morphological scores (P < 0.001). Thalidomide reduced the morphological score (P < 0.002) and seizure grade (P < 0.001), whereas increased seizure onset (P < 0.001) in the arthritis group. There was an increase in malondialdehyde levels in the brain of thalidomide-treated groups (P < 0.002) and a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. There was neither improvement in seizure nor any significant changes in lipid peroxidation and antioxidant enzyme levels in etoricoxib-treated group. Thalidomide was effective in reducing the extent of arthritis as well as reducing the seizure scoring and increasing seizure onset in the adjuvant arthritis group. As it increased lipid peroxidation and reduced SOD and GPx, further evaluation is necessary with respect to oxidative stress.

Pharmacokinetic and toxicological profile of artemisinin compounds: an update.

Artemisinin has been used effectively in malaria treatment. With the emerging resistance to malaria, the optimum and judicial use of the drug has become important. The drug metabolism and toxicology can have an impact on the therapeutic profile and clinical use of this antimalarial agent. In this review, we discuss the pharmacokinetics and toxicological aspects of artemisinin and its therapeutic implications. Artemisinins have several dosing routes including oral, intramuscular, intravenous and rectal. With repeated dosing, artemisinin has propensity for autoinduction, leading to decreased plasma levels on repeated dosing. Combination with other antimalarials in most cases did not influence the pharmacokinetics of artemisinins. Interactions with cytochrome P(450) inhibitors are known but these neither affect the efficacy nor the toxicity of the respective derivative. Artemisinins are generally regarded to be of low toxicity. Two major problems associated with them are neurotoxicity and reproductive toxicity. But the extent of this neurotoxicity is dependent on the nature of the compound, on the route of administration, and on the nature of the formulation. Moreover, it occurs in humans at very high doses. However, as a matter of precaution, the use of artemisinins in the first trimester of pregnancy has been contraindicated.

Recent advances in the pharmacotherapy of chronic anal fissure: an update.

Surgical sphincterotomy reduces anal tone and sphincter spasm and promotes ulcer healing. Because the surgery is associated with the side effect of faecal incontinence, pharmacological agents to treat chronic anal fissure have been explored recently. Glyceryl trinitrate (GTN) ointment (0.2%) has an efficacy of up to 68% in healing chronic anal fissure, but it is associated with headache as the major and most common side effect. Though botulinum toxin injected into the anal sphincter healed over 80% of chronic anal fissures, it is more invasive and expensive than GTN therapy. Diltiazem ointment achieved healing of chronic anal fissure comparable to 0.2% GTN ointment but was associated with fewer side effects. Other drugs that have been tried are lidocaine, the alpha-adrenergic antagonist indoramin, and the potassium channel opener minoxidil.