COVID-19 in Cancer Patients From New York City: A Comparative Single Center Retrospective Analysis.

In this retrospective study we analyze and compare clinical characteristics and outcomes of patients with and without cancer history who were infected with novel coronavirus disease 19 (COVID-19). Medical records were reviewed and a comparative analysis of 53 cancer and 135 non-cancer patients with COVID-19 were summarized. Results: The median age for COVID-19 patients with and without cancer was 71.5 and 61.6 years, respectively. Patients aged 60 years and above were 86.8% and 60.7% in cancer and non-cancer groups, respectively. A high proportion of cases were seen in African Americans 73.6% (with cancer) and 75.6% (without cancer) followed by Hispanic patients. Male and female patients had a high percentage of prostate (39.3%) and breast (32%) cancer respectively. Prostate cancer (18.9%) and myeloma (11.3%) were common among solid and hematological cancers respectively. Hypertension and smoking were prevalent among cancer (83% and 41.5%) compared to non-cancer (67.4% and 9.6%) patients. The common symptoms in cancer patients were dyspnea (64.2%) followed by fever and cough (50.9%) compared to fever (68.1%) and cough (66.7%) in non-cancer patients. Cancer patients had higher levels of lactic acidosis, C-reactive protein, lactate dehydrogenase, and alkaline phosphatase than non-cancer patients (p < 0.05). Conclusions: Rapid clinical deterioration was seen in cancer patients who were aged 60 years and above. Higher mortality was seen in this subgroup, especially when they had associated hypertension and elevated levels of CRP and LDH.

Low morbidity and mortality with COVID-19 in sickle cell disease: A single center experience.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection, which evolved into a global pandemic within a short time. Individuals with sickle cell disease (SCD) suffer from underlying cardiopulmonary comorbidities and are at risk of severe complications such as pneumonia, acute chest syndrome, thrombosis, stroke, and multiorgan failure. Whether COVID-19 poses a high risk of morbidity and mortality in SCD patients remains unclear. Patients with SCD and COVID-19 can present with overlapping clinical features such as respiratory symptoms with ground-glass infiltrates, hyperinflammatory state, and increased risk of thromboembolism. This highlights the need to maintain a low threshold for testing for COVID-19 infection among symptomatic and hospitalized SCD patients. We report a case series of nine hospitalized SCD patients diagnosed with COVID-19 from March 18, 2020 to April 30, 2020 at a tertiary medical center in New York City. The mean age of the study population was 27.9 years, and interval since onset of symptoms and hospital presentation was 1-2 weeks. All patients in our series improved and were discharged home. This limited study shows that SCD patients, who are perceived to be high risk, maybe somehow protected from severe symptoms and complications of COVID-19 infection.

Surface-Modified G4 PAMAM Dendrimers Cross the Blood-Brain Barrier Following Multiple Tail-Vein Injections in C57BL/6J Mice.

Intracranial injections are currently used to deliver drugs into the brain, as most drugs cannot cross the blood-brain barrier (BBB) following systemic injections. Moreover, multiple dosing is difficult with invasive techniques. Therefore, viable systemic techniques are necessary to facilitate treatment paradigms that require multiple dosing of therapeutics across the BBB. In this study, we show that mixed-surface fourth-generation poly(amidoamine) (PAMAM) dendrimers containing predominantly biocompatible hydroxyl groups and a few amine groups are taken up by cultured primary cortical neurons derived from mouse embryo. We also show that these dendrimers cross the BBB following their administration to healthy mice in multiple doses via tail-vein injections and are taken up by neurons and the glial cells as evidenced by appropriate staining methods. Besides the brain, the dendrimers were found mostly in the kidneys compared to other peripheral organs, such as liver, lungs, and spleen, implying that they may be readily excreted, thereby preventing potential toxic accumulation in the body. Our findings provide a proof-of-concept that appropriate surface modifications of dendrimers provide safe, biocompatible nanomaterial with the potential to deliver therapeutic cargo across the BBB into the brain via multiple tail-vein injections.

Molecular, cellular and functional events in axonal sprouting after stroke.

Stroke is the leading cause of adult disability. Yet there is a limited degree of recovery in this disease. One of the mechanisms of recovery is the formation of new connections in the brain and spinal cord after stroke: post-stroke axonal sprouting. Studies indicate that post-stroke axonal sprouting occurs in mice, rats, primates and humans. Inducing post-stroke axonal sprouting in specific connections enhances recovery; blocking axonal sprouting impairs recovery. Behavioral activity patterns after stroke modify the axonal sprouting response. A unique regenerative molecular program mediates this aspect of tissue repair in the CNS. The types of connections that are formed after stroke indicate three patterns of axonal sprouting after stroke: reactive, reparative and unbounded axonal sprouting. These differ in mechanism, location, relationship to behavioral recovery and, importantly, in their prospect for therapeutic manipulation to enhance tissue repair.

Intracerebral hemorrhage in mouse models: therapeutic interventions and functional recovery.

There has been strong pre-clinical research on mechanisms of initial cell death and tissue injury in intracerebral hemorrhage (ICH). This data has led to the evaluation of several therapeutics for neuroprotection or the mitigation of early tissue damage. Most of these studies have been done in the rat. Also, there has been little study of the mechanisms of tissue repair and recovery. This review examines the testing of candidate therapeutics in mouse models of ICH for their effect on tissue protection and repair. This review will help the readers compare it to the extensively researched rat model of ICH and thus enhance work that are pending in mouse model.

Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.

Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus.

Lentivirus-mediated chronic expression of dominant-negative CREB in the dorsal hippocampus impairs memory for place learning and contextual fear conditioning.

Extensive research has shown that the transcription factor CREB has an important role during memory formation. In the present study, we tested a new method for chronic, stable expression of a dominant-negative form of CREB (mCREB) in the dorsal hippocampus using lentiviral vectors. In specific, we tested whether lentivirus-mediated chronic expression of mutant CREB impairs memory for two hippocampus-dependent tasks - place training in the water maze and contextual fear conditioning. Two weeks following intra-hippocampal infusion, experimental (mCREB) and control (LacZ and saline) rats were trained for 30 trials in one session on a place task in a water plus-maze and tested for an additional 30 trials on day 2 and on day 7. On day 8, all rats were trained on a contextual fear conditioning task and tested 24h later. For place learning, there was no difference between treatment groups on day 1, indicating that treatment with the lentiviral vectors did not alter performance or acquisition of the task. In comparisons with controls, mCREB-treated rats were not significantly impaired on day 2, overall, but they showed significant impairment on day 7. Contextual fear memory was impaired in mCREB-infused rats in comparison with controls. At the end of the experiment, total CREB and phosphorylated CREB protein were measured by western blot. Levels of total CREB were increased by approximately 40% among mCREB-treated rats in comparisons with controls, whereas levels of pCREB did not differ between groups, suggesting that the treatment caused significant expression of mCREB. In addition, mCREB infused rats showed a significant reduction in the pCREB to CREB ratio in comparison with controls, suggesting that the memory deficit seen in mCREB rats is most likely due to disruption of gene regulation caused by expression of mutant CREB. Taken together, the present results show that lentivirus expressing mCREB can be used to effectively alter CREB function within the hippocampus and that the treatment impairs memory for hippocampus-dependent tasks.