Feeding on stressed algae exerts important effects on life history traits of Daphnia magna in a multi-stressor environment.

Freshwater ecosystems are increasingly exposed to anthropogenic eutrophication, including high nitrogen. In addition, climate change is leading to more intense and frequent heatwaves, which have enormous impacts on all trophic levels of the ecosystem. Any change in the lower trophic levels, e.g., the phytoplankton, also introduces stress to higher trophic levels e.g., the zooplankton crustacean Daphnia. Individual effects of heatwaves, high nitrate, and changing feed quality have been studied in daphnia, but less is known about their interactive effects. This study used a 3 × 3 × 2 factorial design in which daphnia were exposed to combinations of ecologically relevant nitrate concentrations (0, 50, or 200 mg/L) and different heatwave scenarios (no, short-moderate, or long-intense) in which individuals were either fed with microalgae (P. subcapitata and C. reinhardtii) grown at 20 °C and 50 mg/L nitrate (control feed) or the same conditions as daphnia was exposed to (experimental feed). Throughout the experiment, the interactive effects of high nitrate, heatwave, and feed on mortality, maturation, offspring, and body size were evaluated. In general, heatwaves shorten the lifespan of daphnia. Exposing daphnia to a long-intense heatwave combined with high nitrate resulted in poor performance. In the nitrate-limited condition, however, the restricted proliferation of microalgae reduced feed availability, which also had a major impact on daphnia's life history traits. Daphnia cultured in high nitrate and fed control feed performed better than when fed experimental feed, suggesting that in a high nitrate condition, the microalgae grown under the same experimental conditions was either unable to meet energy requirements or introduced extra stress for the daphnia. Most importantly, the effect of nitrate and heatwave as stressors on the availability and quality of the feed had a greater impact on daphnia than its direct impact. Interestingly, a transgenerational adaptation to nitrate was observed which may help to maintain ecological balance in the long run.

Synergistic effect of nitrate exposure and heatwaves on the growth, and metabolic activity of microalgae, Chlamydomonas reinhardtii, and Pseudokirchneriella subcapitata.

Aquatic biota are threatened by climate warming as well as other anthropogenic stressors such as eutrophication by phosphates and nitrate. However, it remains unclear how nitrate exposure can alter the resilience of microalgae to climate warming, particularly heatwaves. To get a better understanding of these processes, we investigated the effect of elevated temperature and nitrate pollution on growth, metabolites (sugar and protein), oxidative damage (lipid peroxidation), and antioxidant accumulation (polyphenols, proline) in Chlamydomonas reinhardtii and Pseudokirchneriella subcapitata. The experiment involved a 3 × 3 factorial design, where microalgae were exposed to one of three nitrate levels (5, 50, or 200 mg L-1 NO3-l) at 20 °C for 2 weeks. Subsequently, two heatwave scenarios were imposed: a short and moderate heatwave at 24 °C for 2 weeks, and a long and intense heatwave with an additional 2 weeks at 26 °C. A positive synergistic effect of heatwaves and nitrate on growth and metabolites was observed, but this also led to increased oxidative stress. In the short and moderate heatwave, oxidative damage was controlled by increased antioxidant levels. The high growth, metabolites, and antioxidants combined with low oxidative stress during the short and moderate heatwaves in moderate nitrate (50 mg L-1) led to a sustainable increased food availability to grazers. On the other hand, long and intense heatwaves in high nitrate conditions caused unsustainable growth due to increased oxidative stress and relatively low antioxidant (proline) levels, increasing the risk for massive algal die-offs.

Pathology of breast cancer metastasis and a view of metastasis to the brain.

Despite the advances in diagnosis and management of breast cancer, metastasis has been responsible for the staggering percentage of breast cancer-related death. Mortality threat can be explained mostly by the lack of proper understanding of the diversity of pathological features and underlying mechanism of breast cancer metastasis and effective targeted therapy. Breast cancer stem cells (BCSCs) are the potential source of tumor cells spread to distant organs. BCSCs targeted therapy can suppress the breast cancer progression to metastasis. Spreading of tumor cells to the bone, lung, liver, and brain occurs through a distinct non-random process; called metastasis organotropism. Recently, brain metastasis in breast cancer patients has been detected more frequently, causing a significant clinical burden. BRCA1 and BRCA2 associated breast cancers carry a remarkably higher propensity of CNS metastasis. BRCA1 and BRCA2 associated breast cancers commonly have the propensity to be the triple-negative (TN) and hormone receptors (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative molecular subtypes, respectively. Regardless of molecular subtypes, metastasis is most commonly evident at the bone. Heterogeneity is a critical pathological feature, leads to therapeutic resistance. BCSCs, biomarkers expression patterns, and mutations contribute to heterogeneity. In this paper, we discuss crucial pathological features of breast cancer metastasis, emphasizing metastasis organotropism and heterogeneity; and mechanisms of breast cancer metastasis, highlighting the pathways of metastasis to the brain. We consider that this paper reinforces future research areas and benefits the general readers, physicians, and researchers to identify potential areas to develop targeted therapies.

Substance Use Disorders in Patients With Parkinson's Disease and Adverse Hospitalization Outcomes: A National Inpatient Study.

Objectives To understand the demographic pattern of substance use disorders (SUD) in Parkinson's disease (PD) inpatients and to evaluate the impact of SUD on hospitalization outcomes including the severity of illness, length of stay (LOS), total charges, and disposition to nursing facilities. Methods We used the nationwide inpatient sample and identified adult patients (age, ≥40 years) with PD as a primary diagnosis and comorbid SUD (N = 959) and grouped by co-diagnosis of alcohol (N = 789), cannabis (N = 46), opioid (N = 30), stimulants (N = 54) and barbiturate (N = 40) use disorders. We used a binomial logistic regression model to evaluate the odds ratio (OR) for major loss of functioning and disposition to nursing facilities in PD inpatients. All regression models were adjusted for demographics, including age, sex, race, and median household income. Results Alcohol, opioid, and stimulant use disorders were prevalent in old-age adults (60-79 years), males, and whites, but cannabis use was prevalent in middle-aged adults (40-59 years), and barbiturate use among older-age (>80 years). The severity of illness is statistically higher in PD inpatients with comorbid opioid and barbiturate use disorders with major loss of body functioning, closely seconded by alcohol and stimulant use disorder cohorts (27.6% and 25.9%, respectively). Disease severity and loss of body functioning increase with advancing age (>80 years adults, OR 5.8, 95%CI 5.32-6.37), and in blacks (OR 1.7, 95%CI 1.56-1.81), and those with opioid use disorder (OR 3.8, 95%CI 1.96-7.35). PD inpatients with barbiturate use disorder had a higher LOS and charges by 17.4 days and $68,922, and six-fold increased likelihood (95%CI 2.33-15.67) for disposition to nursing facilities. Conclusions SUD is prevalent among PD patients and is associated with more severe illnesses with body loss functioning and prolonged care. A multidisciplinary care model including collaborative neuropsychiatric and addiction management is required to manage SUD among PD patients to lessen disease severity, slow down the disease progression and potentially save medical costs.

Psychiatric Comorbidities in Pediatric Inpatients With Human Immunodeficiency Virus Infection and Impact on Hospital Course: Inputs From a Case-Control Inpatient Study.

Objectives In this study, we aimed to delineate psychiatric comorbidities in pediatric inpatients with versus without human immunodeficiency virus (HIV) infection and to measure its impact on the length of stay (LOS) and cost of treatment during hospitalization. Methodology We conducted a case-control study using the Nationwide Inpatient Sample and included 4,920 pediatric inpatients between the ages of six and 18 years who were sub-grouped by a comorbid diagnosis of HIV (N = 2,595) and non-HIV (N = 2,325) and matched for demographics (age, sex, and race) by propensity case-control matching. Logistic regression analyses were used to evaluate the adjusted odds ratio (aOR) of association for psychiatric comorbidities (depression, anxiety, post-traumatic stress disorder, psychosis, and drug abuse) in the HIV-positive compared with the HIV-negative (as reference category) pediatric inpatients. We measured the differences in the LOS and cost using the independent sample t-test. Results We found that the most prevalent psychiatric comorbidities in the HIV-positive group were anxiety (6.9%), drug abuse (6.6%), psychosis (6.4%), and depression (6.2%). The HIV-positive group had a significantly higher likelihood of comorbid psychosis (aOR: 1.82; 95% confidence interval [CI]: 1.38-2.40) and depression (aOR: 1.79; 95% CI: 1.36-2.36). The mean LOS per hospitalization episode was longer for the HIV-positive group (11.1 days vs. 6.0 days; P < 0.001) compared to the HIV-negative pediatric inpatients. Conclusions We found an increased risk of depression by 79% and psychosis by 82% in the HIV-positive pediatric population. These inpatients also had an extended hospitalization stay (by five days), adding to the healthcare economic burden.

Seroconversion and Skin Mucosal Parameters during Koi Herpesvirus Shedding in Common Carp, Cyprinus carpio.

Seroconversion and the mucosal lysozyme G (lysG), complement 3 (c3), and immunoglobulins M (IgMsec) and Z2 (IgZ2) were measured for up to 900 degree days (DD) in skin swabs from common carp exposed to koi herpesvirus (KHV or CyHV-3) at either a non-permissive temperature (12 °C) or permissive temperatures (17 and 22 °C), and in survivors subjected to temperature increase to 22 °C 500 DD after the initial exposure. The survival rate at 22 °C varied from 100% in fish initially exposed at 12 °C, to 20% at 17 °C and 0% at 22 °C. Viral shedding episodes lasted for up to 29 days (493 DD) for fish clinically infected at 17 °C, and up to 57 days (684 DD) for asymptomatic fish held at 12 °C. Up-regulation of lysG transcripts was measured at 17 and 22 °C. Down-regulation of c3 and IgMsec transcripts was measured independent of the water temperature, followed by up-regulation after the temperature increase coinciding with seroconversion and clearance of KHV from the skin mucus. IgZ2 mRNA showed a negative correlation with IgM transcripts. KHV subversion of the complement system at the mucosal site coupled with poor immunoglobulin secretion during the viral replication might contribute to the long window of viral shedding, thus facilitating viral transmission.

Demographics and Hospital Outcomes in American Women With Endometriosis and Psychiatric Comorbidities.

Objectives To explore sociodemographic differences and hospital outcomes in endometriosis patients with versus without psychiatric comorbidities. Methods We conducted a cross-sectional study using the Nationwide Inpatient Sample (NIS, 2012-2014), and included 63,160 females with primary diagnosis of endometriosis. We used descriptive statistics and Pearson's chi-square test to measure the differences in demographics and utilization of gynecologic procedures by the presence of psychiatric comorbidities. Results Psychiatric comorbidities were present in 18.7% inpatients with endometriosis. About three-fourth of these inpatients were in reproductive age group 26-45 years (75.7%) and were whites (79.1%). Psychiatric comorbidities were seen more in females from middle-income families and from the midwest region of the US. There was no significant difference in the utilization of gynecological procedures by the presence of psychiatric comorbidities. However, inpatients with psychiatric comorbidities had a longer mean length of stay (2.5 vs. 2.3 days) and total charges ($35,489 vs. $34,673) compared to the non-psychiatric cohort. Anxiety disorders predominated at 45% in patients with endometriosis followed by depressive disorder (31.3%), psychotic disorders (12.3%), and drug abuse (6.3%). Conclusion Endometriosis with psychiatric comorbidities is prevalent in young white females from a middle-income family. Anxiety and depressive disorders are most prevalent and are associated with extended hospitalization stay and higher charges, thereby negatively impacting the healthcare burden compared to those without psychiatric comorbidities.