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Aim: The present study aimed to isolate and characterize chemical compounds from Anthocephalus cadamba Miq. bark and evaluate their anticancer activity by in silico, molecular docking, and in vitro studies. Background: Anthocephalus cadamba is a traditionally used Indian medicinal plant. The anticancer and phytochemical properties of this plant remain unexplored except for a few studies. Objectives: The objective of the study was to evaluate the antiproliferative activity of extract and fractions against breast cancer and prostate cancer cell lines and isolate and characterize active compounds from bio-active guided fractions. Moreover, the anticancer activity of isolated compounds against breast and prostate cancer cell lines was also evaluated, in addition to in silico and molecular docking interactions of isolated compounds with VEGFR2 and PDGFRα target proteins. Methods: The compounds were isolated and purified with the help of repeated column chromatography, and spectral techniques, such as 1D, 2D NMR, and GC-MS/MS, were used to identify and elucidate the structure of the compounds. Moreover, prediction of activity spectra for substances, physiochemical properties, bioactivity radar prediction, bioactivity score, natural-product likeness, ADME, and toxicity parameters of isolated compounds (AC-1 to AC-4) was performed through various in-silico databases and servers. To evaluate the docking interaction profile and binding energies of compounds, three docking tools were utilized, such as AutoDock, AutoDock Vina, and iGEMDOCK, against two targets VEGFR2 and PDGFRα. MD simulation was performed through ligand and receptor molecular dynamic server (LARMD). Results: It was found that the A. cadamba bark chloroform fraction demonstrated a significant inhibitory effect against MDA-MB-231, MCF-7, and PC-3 cells in a dose-time-dependent manner. The bioassay-guided isolation afforded four molecules AC-1 to AC-4 from chloroform fraction. Moreover, the GC-MS/MS profiling identified fourteen new molecules which were not reported earlier from A. cadamba. The in-silico study showed that the isolated compounds (AC-1 to AC-4) followed Lipinski’s rule and had good oral bioavailability. While compound AC-4 had positive bioactivity scores except for kinase inhibitor activity. The ADMET profiling revealed that AC-4 was non-toxic and easily absorbed in the human intestine, and transportable in the blood-brain barrier compared to AC-1, AC-2, AC-3, and standard drug doxorubicin. Molecular docking and MD simulation assessment also signified AC-4 anticancer activity with dual inhibitory action against the target proteins VEGFR2 and PDGFRα amongst the studied compounds. The in vitro cell viability assay of isolated compounds demonstrated that AC-1 showed IC50 (μg/mL) value of 34.96 ±3.91, 47.76±3.80 69.1±4.96, AC-2; 68.26±4.22, 54.03±5.14, >100, AC-3; 35.34±4.14, 51.5±51.5, 70.8±5.25 and AC-4; 44.2±3.57, 24.2±2.67, 51.2±2.54 for MDA-MB-231, MCF-7, and PC-3 cancer cell lines, respectively and compared with standard drug doxorubicin. Moreover, fluorescence microscopy confirmed the apoptogenic property of compounds. We also found that AC-4 exhibited significant intracellular ROS production in breast cancer cells, thereby inducing apoptosis and eventually cell death. Conclusion: In conclusion, A. cadamba afforded four pure molecules AC-1 to AC-4 with the identification of fourteen new compounds. The entire in-silico studies concluded that the AC-4 compound had better oral bioavailability, bioactivity score, and ADMET profile among studied molecules. Molecular docking analysis and MD simulation also supported AC-4 dual inhibitory action against both VEGFR2 and PDGFRα receptors. Moreover, the isolated molecules AC-1, AC-2, AC-3, and AC-4 were found to be active against MDA-MB-231, MCF-7, and PC-3 cancer cells. The molecule AC-4 was found to induce ROS-mediated apoptosis in breast cancer cells. It was found that the anticancer inhibitory potentiality of AC-4 is directed to its molecular stereochemistry which specifically binds to the target proteins of breast cancer cells with no toxicological effect. Therefore, AC-4 is suggested to be an effective aspirant for novel drug design and discovery.

Hepatocellular carcinoma (HCC) is the third prominent cause of cancer mortality, with increasing prevalence and poor survival worldwide. Being diagnosed at an advanced stage, HCC frequently results in poor prognosis, treatment failure, and recurrence. Post-treatment reactivation and recurrence often amplify the immunosuppressed state induced by HCC pathogenesis. Therefore, stimulating the immune system may be a potential therapy measure for the treatment of HCC. Immune responses of the body may be potentiated by modulation of various effector cells such as B-cells, T-cells, Treg cells, natural killer cells, dendritic cells, cytotoxic T-lymphocytes, and other antigen-presenting cells. microRNAs (small non-coding RNAs) are the regulators of gene expression via translational inhibition or mRNA degradation. Various activities and developmental stages of the immune system are governed by miRNAs and they have a regulative impact on innate and adaptive immune cells in both, healthy and diseased conditions. Their misexpression has been associated with the initiation, development, and metastasis of various cancer types, including HCC. This review summarizes the functional impact of these immuno-miRNAs in the improvement of tumor conditions.

BACKGROUND: Fibromyalgia syndrome (FMS) is an extra-articular rheumatological disease characterised by widespread chronic musculoskeletal pain. Metal-induced oxidative stress contributes to the severity of FMS. AIMS: First, this study evaluated the association between plasma levels of toxic heavy metals and essential metals with oxidative stress (OS) markers. Second, the OS markers and metal contents were correlated with the disease severity by assessing the Fibromyalgia Impact Questioner Revised (FIQR) and tender points (TP). METHOD: A total of 105 FMS patients and 105 healthy controls of similar age and sex were recruited. OS parameter such as lipid peroxidation (LPO), protein carbonyl group (PCG), nitric oxide (NO) and essential metals such as zinc (Zn), magnesium (Mg), manganese (Mn), copper (Cu) and toxic heavy metals such as aluminium (Al), arsenic (As), lead (Pb) were estimated. RESULTS: Levels of LPO, PCG, NO (p< 0.001) and Cu, Mn, and Al (p< 0.001), were significantly higher, and Mg (p< 0.001) and Zn (p< 0.001) were significantly lower in patients compared to controls. A positive association was observed between OS parameters, FIQR and TP with Cu, Al and Mn. A significant negative association was observed between Zn and Mg with FIQR, TP and OS parameters. CONCLUSION: Heavy metals such as Al induce OS parameters and decrease the levels of essential trace elements such as Mg and Zn, which may be responsible for the severity of FMS.

With the onset of the COVID-19 outbreak there has been concern that patients with obstructive sleep apnea (OSA) who develop COVID-19 may be at risk of greater morbidity and mortality than patients without OSA. COVID-19 is associated with an increased mortality in the elderly and particularly those with obesity, hypertension and diabetes, features which are typically seen in patients with OSA. This article describes the COVID-19 environment in New York City in which patients were evaluated and treated for OSA. A telephone questionnaire survey of 112 OSA patients determined the occurrence of COVID-19 in the sleep apnea population and the patients’ perspective on sleep apnea Positive Airway Pressure (PAP) management during the COVID-19 outbreak. The three main objectives of the survey were as follows: 1) To discover how patients were coping with COVID-19 pandemic in terms of their sleep apnea and PAP use, 2) To determine whether PAP usage changed after the onset of the outbreak in terms of adherence, and 3) To find out if patients were concerned about whether they were at greater risk of contracting COVID-19 because of their sleep apnea and, if they became infected, whether COVID-19 might result in greater complications because of the presence of sleep apnea. The adjustment in clinical management of OSA patients is described both during the peak of the outbreak in NYS, as well as the proposed modifications that will be instituted in order to return to full sleep center activities., Highlights • Common OSA comorbidities such as hypertension, diabetes mellitus and obesity, overlap with those of patients who die of COVID-19 complications and the interaction needs further research. • Treating OSA patients with PAP during the COVID-19 pandemic requires careful management to reduce patient concerns and optimize patient care. • Safety measures to minimize exposure and dissemination of COVID-19 by PAP therapy should be instituted by sleep centers during both the peak of the epidemic and at centers reopening.

Objectives Limited treatment options are available for advanced stages of chronic myeloid leukaemia (CML). Moreover, patients’ relapse after a short remission period, which prompts them to identify a potent drug with the least toxicity. An Unani herbal formulation, Itrifal-e-Aftimoon (IEA) is used for certain neurological disorders, however, its antitumor potential has not been reported yet in any malignancy, including CML. Methods The aqueous extract of IEA was characterized by HPLC/LC-MS and used alone or in combination with standard drug, imatinib in CML cell lines (K562, KU812) in vitro to assess its effect on cancer-associated parameters such as cytotoxicity, cell cycle, apoptosis, oxidative stress, inflammation, angiogenesis, and certain signalling pathways. Results LC–MS characterization of IEA showed the presence of antitumor compounds including catechin and caffeic acid. Treatment with IEA caused cytotoxicity and arrested cells in the sub-G0/G1 phase. Subsequent assays confirmed apoptosis-mediated cell death with mitochondrial membrane depolarization and alleviation of oxidative stress. IEA abrogates IL-6, VEGF, angiopoietin-2, and alters Th1/Th2 cytokines. IEA potentiated the effect of imatinib even at lower doses by affecting FAK/STAT/Akt/ERK pathways. Conclusion IEA possesses antitumor potential against CML and increases the efficacy of imatinib when used in combination, suggesting utilization of IEA as an adjuvant therapy for better management of CML in the future.

COVID-19 has involved numerous countries across the globe and the disease burden, susceptible age group; mortality rate has been variable depending on the demographical profile, economic status, and health care infrastructure. In the current clinical environment, COVID-19 is one of the most important clinical differential diagnoses in patients presenting with respiratory symptoms. The optimal mechanical ventilation strategy for these patients has been a constant topic of discussion and very importantly so, since a great majority of these patients require invasive mechanical ventilation and often for an extended period of time. In this report we highlight our experience with a COVID-19 patient who most likely suffered barotrauma either as a result of traumatic endotracheal intubation or primarily due to COVID-19 itself. We also aim to highlight the current literature available to suggest the management strategy for these patients for a favorable outcome. The cases described are diverse in terms of age variance and other comorbidities. According to the literature, certain patients, with COVID-19 disease and spontaneous pneumothorax were noted to be managed conservatively and oxygen supplementation with nasal cannula sufficed. Decision regarding need and escalation to invasive mechanical ventilation should be taken early in the disease to avoid complications such as patient self-inflicted lung injury (P-SILI) and barotrauma sequelae such as pneumothorax and pneumomediastinum Recent systematic review further supports the fact that the use of non-invasive ventilation (NIV) in certain patients with COVID-19 pneumonia may give a false sense of security and clinical stabilization but has no overall benefit to avoid intubation. While invasive mechanical ventilation may be associated with higher rates of barotrauma, this should not mean that intubation and invasive mechanical ventilation should be delayed. This becomes an important consideration when non-intensivists or personnel with less experience provide care for this vulnerable patient population who may rely too heavily on NIV to avoid intubation and mechanical ventilation.

The current pandemic of COVID-19 has infected around 2.5 million people with more than 125,000 deaths across the globe till date, and numbers are still rising. The causative organism is a virus of corona family. The International Committee on Taxonomy of Viruses (ICTV) named it severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its similarities with the virus was caused SARS outbreak (SARS-CoV). Although most of the patients present with less severe symptoms like rhinitis, cough, fever, and mild flu-like symptoms, it may progress to severe acute respiratory illness, pneumonia or acute respiratory distress syndrome (ARDS) mainly in immunocompromised hosts. Severe infections mainly involve lungs, and compromise its capacity of ventilation. Respiratory and mechanical ventilation is one of the important parts of management.

In 2010, a new study published by the National Lung Screening Trial showed a 20% reduction in mortality for those patients screened with low-dose computed topography (CT) versus x-ray. Recently, the Centers of Medicare and Medicaid have agreed to cover this service for those patients who meet the screening criteria. We compare the outcomes and costs associated with developing and implementing a lung cancer screening program. One thousand sixty-five patients were screened from January 2014 to December 2014. These patients were screened on a low-dose CT screening protocol throughout Beaumont Health System. The American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) were used to assign the score for each patient. Screening eligibility criteria were based on the National Comprehensive Cancer Network guidelines. Downstream activity and revenue was determined after initial low-dose CT screening. At 1 year, 20 patients (1.6%) were diagnosed with lung cancer and another 15 patients were diagnosed with another form of cancer after screening. The median age, packs per day, and pack years smoked for all patients was 63, 1.0, and 39.0 years, respectively. Lung-RADS scores for all patients was 18% (1), 24.1% (2), 6.3% (3), and 5.4% (4). The net revenue for all activity after screening was $3.2 million. The establishment of a low-dose CT lung cancer screening program improved the ability to screen patients as demonstrated by the number of patients screened and those diagnosed with a malignancy. These findings were also consistent with the findings from the National Lung Screening Trial study.

Background and objective Electronic cigarettes (e cigarettes) are battery operated devices that produce aerosol by heating a solution typically made up of nicotine, propylene glycol, glycerin and flavouring agents. The use of e cigarettes has risen dramatically in recent years especially among adolescents and young adults. These devices have been marketed as safer alternatives to tobacco smoking by their manufactures despite lack of adequate safety data. Methods We present a case of 40-year-old female patient who developed significant pulmonary toxicity secondary to e cigarette use and searched existing literature relevant to the case. Results To our knowledge this is the second reported case of organizing pneumonia and tenth reported case of pulmonary toxicity related to e cigarette use. Our patient presented with symptoms of worsening dyspnoea and intermittent chest pain for past 1 month. She reported increased use of e cigarettes during this time period to help her quit smoking. Patient developed acute hypoxemic respiratory failure requiring intubation and mechanical ventilation. She was diagnosed with organizing pneumonia on open lung biopsy and was successfully treated with steroids along with abstinence from e cigarette use. Conclusions As the current data on health effects of e cigarettes is limited, case reports can serve important piece of information in this regard. The use of e cigarettes has increased exponentially in recent years and continue to rise; therefore, physicians should be aware of adverse effects and toxicity related to its use.

Dietary components present in foods, spices and herbs are source of natural compounds viz. phenols, flavonoids, tocopherols, ascorbic acid and carotenoids with potential benefits. Ginger is one such herb commonly used throughout the world as a spice for dietary as well as medicinal purpose since ancient period. Here, we investigated the methanolic extract of Zingiber officinale rhizome (ZOME) for anticancer activity against human cervical cancer HeLa cells and breast cancer MDA-MB-231 cells and antioxidant activity using 1,1-diphenyl-2-picryl hydroxyl (DPPH) scavenging assay, 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS) cation decolorization test. Antiproliferative activity was substantiated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assay for cell viability and cell proliferation, Hoechst staining was performed to examine apoptosis. Our results demonstrated that ZOME inhibited the proliferation and colony formation in HeLa and MDA-MB-231 cells, in a dose- and time-dependent manner and induced typical changes in nuclear morphology, chromatin condensation and fragmentation, membrane shrinkage and blebbing in both cells indicated apoptotic property of Z. officinale. ZOME exhibited potent antiradical activity against DPPH and ABTS. On the basis of the results of the present study, it may be suggested that Z. officinale has promising anticancer and antioxidant properties. Since, Z officinale has been commonly used throughout the world as a spice for dietary as well as for medicinal purposes since prehistoric times. Therefore, enriched use of Z. officinale as dietary material could be recommended in ethno-medicine for the management of cervical and breast cancers. Moreover, further studies are needed to isolate and characterize the potent compounds for further adjuvant therapy against such malignancies.

Solanum nigrum is a traditional Indian plant acclaimed for its medicinal properties since antiquity. Among all plant parts fruit berries have shown to be most pharmacologically active part. In the present investigation, we tried to characterize the bioactive principles of chloroform fraction of S. nigrum (CFSn) fruit berries using GC-MS analysis. We could identify 29 compounds belonging to different chemical classes viz. alkaloids, flavonoids, carbohydrates, glycosides, phytosterols, proteins, phenolic compounds, and saponins. More specifically, we found two novel phenolic compounds, benzoiisovanillin and syringic acid (4-hydroxy-3, 5-dimethoxybenzoic acid), which may be responsible for its pharmacological properties. Our phytochemical investigation of CFSn was well supported by its total phenolic content and antioxidant activity which we evaluated subsequently. Further, we investigated the anticancer activity against breast cancer cell lines (MDA-MB-231 and MCF-7) as well. Our in vitro results indicated that CFSn exhibited significant antiproliferative activity against both these cell lines and due induction of cancer cell death through apoptosis. Our study emphasizes the need for isolation and characterization of specific bioactive compounds of CFSn and determination of their mechanism of action responsible for its anticancer activity in breast cancer cells.

The inevitable development of chemoresistance and unmanageable side effects are the major therapeutic challenges in management of breast cancer imposing an urgent need for identification of novel therapeutic agents. In the present investigation, we report anti-proliferative activity of chloroform fraction of

Isolated pleural effusion is a very rare presentation of malignant melanoma. A 46 year-old male patient presented to us with complaints of shortness of breath during the previous month. A contrast enhanced computed tomography (CECT) imaging scan of his thorax showed right-sided pleural effusion with the absence of any mass lesion or mediastinal lymphadenopathy. Cytology of his pleural fluid showed pigmented cells suggestive of malignant melanoma. Staining of the pleural fluid cells with immunohistological markers for melanoma (HMB 45 and S 100) were positive. An examination of his skin did not reveal any pigmented lesion, nor was there a past history of malignant melanoma for this patient. The patient responded well to therapy for malignant melanoma and has remained asymptomatic for the last year. This patient was diagnosed with a rare case of primary malignant melanoma of the pleura presenting as isolated pleural effusion.

The authors present the case of a young child with "fou rire prodromique" as an initial manifestation of pontine tuberculoma. This report is the first description of fou rire prodromique as the presenting sign of CNS tuberculosis. The combination of clinical information and CT findings allowed for precise localization of the lesion and suggested tuberculoma as the possible etiology.

Extraosseous Ewing sarcoma is a rare soft tissue tumour that is histologically indistinguishable from the bone Ewing sarcoma. The translocation involving chromosome 22 along with CD 99 expression is pathognomonic and is useful in differentiating from other small round cell tumours. Primary lung involvement by this malignant tumour is very uncommon and up to this date only ten cases have been reported. We report a further case in a 15 year-old-female who presented with a huge lung mass causing an opaque haemithorax.

We studied the feasibility of implementing a community-based participatory process (CBPP) that addressed cancer education, prevention, and screening in 2 ethnic minority populations by evaluating the improvement in rates of cancer screening compared with historical benchmarks.From 2003 to 2009, 2281 community members participated in CBPPs conducted by the Beaumont Cancer Institute in cooperation with the Arab American and Chaldean (AAC) Council, the National Cancer Institute, and the American Cancer Society. The study population consisted of 1067 individuals who completed a postcancer forum survey: 642 from the African American (AA) and 425 from the AAC forums. Data were collected on participants' screening history and participation in subsequent screening tests after the previous year's CBPP.Following attendance of at least one cancer forum the previous year, 329 (30.8%) of the 1067 participant respondents underwent some type of cancer screening, 32% in the AA forums and 28.9% in the AAC forums. Compared with published controls, the CBPPs led to a 38.6% increase in mammographic screening and a 28.7% increase in prostate-specific antigen screening; the AA cohort had 39.7% and 28.4% increases whereas the AAC cohort had 36.3% and 28.9% increases in mammographic and prostate-specific antigen screening, respectively.The results of this study suggest that implementing CBPPs are feasible in underscreened ethnic minority populations. Further studies need to be performed to determine the absolute benefit of CBPPs compared with baseline levels of screening within these ethnic minority populations.

Hydatid cyst is a disease caused by a parasitic tapeworm, Echinococcus granulosus, and most commonly involves liver and lung. Ruptured pulmonary hydatid cyst can present a diagnostic challenge, and radiograph can be inconclusive. Anaphylactic reaction is a rare complication of ruptured pulmonary hydatid cyst. A 22-year-old male came to our emergency department in shock with symptoms of shortness of breath and altered mental status from the previous day. Radiograph showed a thin-walled circular translucent area in the right upper lung field, which was misdiagnosed as pneumothorax, and an intercostal chest tube was inserted. After 5 days, repeat radiograph revealed a cavity with an air/fluid level. The chest tube was removed and contrast-enhanced computed tomogram showed a cavity with water-lily sign, which suggests ruptured hydatid cyst. Immunoglobin-G enzyme-linked immunosorbent assay for Echinococcus was positive. The patient responded well to treatment with crystalloid infusion, supplemental oxygen, and albendazole, and then underwent surgery. Anaphylactic reaction due to rupture of a hydatid cyst is rare, but hydatid disease should be suspected in patients from areas where Echinococcus is endemic.