Screening of Oral Squamous Cell Carcinoma Through Color Intensity-Based Textural Features.

Background Early screening and diagnosis of oral squamous cell carcinoma (OSCC) has always been a major challenge for pathologists. Artificial intelligence (AI)-assisted screening tools can serve as an adjunct for the objective interpretation of Papanicolaou (PAP)-stained oral smears. Aim This study aimed to develop a handy and sensitive computer-assisted AI tool based on color-intensity textural features to be applied to cytologic images for screening and diagnosis of OSCC. Methodology The study included two groups consisting of 80 OSCC subjects and 80 control groups. PAP-stained smears were collected from both groups. The smears were analyzed in Matlab software computed data and color intensity-based textural features such as entropy, contrast, energy, homogeneity, and correlation, were quantitatively extracted. Results In this study, a statistically significant difference was noted for entropy, energy, correlation, contrast, and homogeneity. It was found that entropy and contrast were found to be higher with a decrease in homogeneity, correlation, and energy in OSCC when compared to the control group. Receiver operating characteristic curve analysis was done and accuracy, sensitivity, and specificity were found to be 88%, 91%, and 81%, respectively. Conclusion The gray-level co-occurrence matrix (GLCM) color intensity-based textural features play a significant role in differentiating dysplastic and normal cells in the diagnosis of OSCC. Computer-aided textural analysis has the potential to aid in the early detection of oral cancer, which can lead to improved clinical outcomes.

COVID-19 booster vaccine uptake and reduced risks for long-COVID: A cross-sectional study of a U.S. adult population.

Long-COVID (having symptoms lasting 3 months or longer post-infection) is an emerging public health concern, yet research on whether COVID-19 booster vaccines can mitigate this condition is limited. This study examined associations between booster uptake and long-COVID prevalence among U.S. adults. Data were analyzed from 8757 adults aged 18 years or older with a history of COVID-19 infection from the 2022 National Health Interview Survey. Weighted prevalence and logistic regression models examined relationships between self-reported COVID-19 booster vaccination status and long-COVID, adjusting for sociodemographics and health factors. 19.5 % reported experiencing long-COVID. Individuals receiving the COVID-19 booster vaccine had significantly lower adjusted odds of long-COVID (OR 0.75, 95 % CI 0.61-0.93) compared to unvaccinated individuals. Overall, these findings suggest that COVID-19 booster vaccination is associated with a reduced prevalence of long-COVID among the U.S. adult population, underscoring the importance of optimizing booster uptake to mitigate the long-term impacts of COVID-19.

Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro.

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that ME-344 could enhance the anti-AML activity of VEN. Here we report that ME-344 enhanced VEN to target AML cell lines and primary patient samples while sparing normal hematopoietic cells. Cooperative suppression of OXPHOS was detected in a subset of AML cell lines and primary patient samples. Metabolomics analysis revealed a significant reduction of purine biosynthesis metabolites by ME-344. Further, lometrexol, a purine biosynthesis inhibitor, synergistically enhanced VEN-induced apoptosis in AML cell lines. Interestingly, AML cells with acquired AraC resistance showed significantly increased purine biosynthesis metabolites and sensitivities to ME-344. Furthermore, synergy between ME-344 and VEN was preserved in these AraC-resistant AML cells. In vivo studies revealed significantly prolonged survival upon combination therapy of ME-344 and VEN in NSGS mice bearing parental or AraC-resistant MV4-11 leukemia compared to the vehicle control. This study demonstrates that ME-344 enhances VEN antileukemic activity against preclinical models of AML by suppressing OXPHOS and/or purine biosynthesis.

The Natural Sweetener Stevia: An Updated Review on its Phytochemistry, Health Benefits, and Anti-diabetic Study.

Stevia rebaudiana Bertoni is one of the significant high qualities of non-caloric sugar substitute sweetener plants against diabetes disease. Diabetes mellitus is one of the most common metabolic diseases caused by insulin secretion defects, insulin resistance in peripheral tissues, or both. Stevia rebaudiana is a perennial shrub of the Compositae family that is grown in several places around the world. It contains a plethora of different bioactive constituents which are responsible for several activities and sweetness. This sweetness is due to the presence of steviol glycosides which is 100-300 times sweeter than sucrose. Furthermore, stevia reduces oxidative stress, lowering the risk of diabetes. Its leaves have been used to control and treat diabetes and a variety of other metabolic diseases. This review summarizes the history, bioactive constituents of S. rebaudiana extract, pharmacology, anti-diabetic activity, and its application, especially in food supplements.

Role of Betel Nut in Liver Toxicity in Oral Submucous Fibrosis and Oral Cancer Patients: A Case-Control Study.

BACKGROUND: In 2004, the International Agency for Research on Cancer (IARC) revised its conclusion that betel quid, both with and without tobacco, as well as areca nut alone, was carcinogenic to humans. Areca nut may enhance chemical hepatocarcinogenesis. Researchers have studied the role of areca nut components in the etiology of oral submucous fibrosis (OSF) for the past two decades. OBJECTIVES: In this, we will study the role of betel nut chewing on the liver and its correlation with the occurrence of OSF and oral cancer. METHODOLOGY: It is a type of case-control study for a duration of three months. A total of 60 subjects were selected based on the selected groups and exclusion criteria. A detailed case history was taken, and after that blood samples were collected for conducting liver function tests. After the collection of reports from the labs, the results were assessed, analyzed, and correlated with the case history of each subject. RESULTS: This research aids in the identification of a link between the occurrence of OSF, oral squamous cell carcinoma (OSCC) liver damage, and the practice of eating betel nuts. Chewing betel quid on a regular basis appears to be a separate risk factor for liver damage, OSCC, and OSF. CONCLUSION: This assessment of liver function with case history in each subject aids in providing an improvised and prioritized method for the early diagnosis of liver misfunctioning in the patient with OSF or Oral Cancer due to a common etiological factor, that is betel nut.

Evaluation of the Efficacy of a Neem Extract-Based Herbal Ointment, Herbal Antioxidant, and Propolis on Oxidative Stress Related to Oral Ulcers: An Interventional Animal Study.

Traumatic oral ulcers are one of the most commonly encountered oral ulcers. Their healing may be delayed due to factors like the presence of opportunistic infectious microbes in the oral cavity, secondary trauma from sharp edges of teeth, and the systemic condition of the patient. AIM: To compare the efficacy of a newly developed neem extract containing herbal ointments (propolis and Hemidesmus indicus) in enhancing the wound contraction of traumatic oral ulcers and to determine the relationship between oxidative stress and oral ulcers. METHOD: Ulcers were inflicted by trauma in the mouths of experimental rabbits using a 5 mm punch biopsy device. Forty-eight animals were randomly put into six groups (n = 12). Group 1 was the control group that did not receive any intervention; Group 2 had a systemic treatment of Hemidesmus indicus extract; Group 3 received a topical application of propolis; Group 4 had a topical application of a neem extract-based herbal ointment; Group 5 was administered a combination of Hemidesmus indicus and propolis; and Group 6 had a combination of a neem-based herbal ointment and Hemidesmus indicus. Oxidative stress levels were calculated by measuring superoxide dismutases and malondialdehyde levels in the blood on days 0, one, seven, and 14. Wound contraction scores of ulcers were also assessed on days seven and 14. RESULTS: Significantly higher wound contraction scores were seen in groups treated with herbal ointment in comparison to groups treated without herbal ointment. Oxidative stress levels increased in all groups after the infliction of ulcers (day one) and then declined as the ulcers healed, reaching near-normal levels on day 14. Groups containing Hemidesmus indicus showed a significant reduction in oxidative stress in comparison to groups without Hemidesmus indicus. A p-value of <0.05 was considered significant. CONCLUSION: A combined formulation of herbal ointment and Hemidesmus indicus proved to be the most efficacious in enhancing wound contraction of oral ulcers along with significantly reducing oxidative stress in experimental rabbits.

Quality in neonatal mortality audits: Results of pilot study from district of Dhule, Maharashtra.

Introduction: As per WHO guidelines, it is important to have quality among mortality audit documents to improve outcome in health services. Objective: To assess quality of facility-based neonatal mortality audits implementation. Methodology: Mixed-method descriptive analysis was conducted. Totally, 96 death review documents were reviewed. The 25 healthcare workers were interviewed in depth. Observation analysis done for audit meetings using WHO modified checklist for quality in audit toolkit. Results: The observation of audit meetings highlighted that almost half of the members were not communicated regarding vision of audit and framework of audit and review meetings. In quantitative analysis, it was found that secondary care hospitals were not having accuracy and consistency in audit documentation. Conclusion: The quality of neonatal death audit was poor due to challenges faced by the hospitals in creating an enabling atmosphere, which can be overcome by sharing the vision of audit with the whole staff of the hospital. A standard operating procedure for audit committee to be adopted to implement action plans. Commitment, investment, and intentional leadership from everyone, including all healthcare workers, can make these ambitious goals attainable.

A Saliva-Based Serological and Behavioral Analysis of SARS-CoV-2 Antibody Prevalence in Howard County, Maryland.

The objective of the study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the Howard County, Maryland, general population and demographic subpopulations attributable to natural infection or coronavirus disease 2019 (COVID-19) vaccination and to identify self-reported social behaviors that may affect the likelihood of recent or past SARS-CoV-2 infection. A cross-sectional, saliva-based serological study of 2,880 residents of Howard County, Maryland, was carried out from July through September 2021. Natural SARS-CoV-2 infection prevalence was estimated by inferring infections among individuals according to anti-nucleocapsid immunoglobin G levels and calculating averages weighted by sample proportions of various demographics. Antibody levels between BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) recipients were compared. Antibody decay rate was calculated by fitting exponential decay curves to cross-sectional indirect immunoassay data. Regression analysis was carried out to identify demographic factors, social behaviors, and attitudes that may be linked to an increased likelihood of natural infection. The estimated overall prevalence of natural infection in Howard County, Maryland, was 11.9% (95% confidence interval, 9.2% to 15.1%), compared with 7% reported COVID-19 cases. Antibody prevalence indicating natural infection was highest among Hispanic and non-Hispanic Black participants and lowest among non-Hispanic White and non-Hispanic Asian participants. Participants from census tracts with lower average household income also had higher natural infection rates. After accounting for multiple comparisons and correlations between participants, none of the behavior or attitude factors had significant effects on natural infection. At the same time, recipients of the mRNA-1273 vaccine had higher antibody levels than those of BNT162b2 vaccine recipients. Older study participants had overall lower antibody levels compared with younger study participants. The true prevalence of SARS-CoV-2 infection is higher than the number of reported COVID-19 cases in Howard County, Maryland. A disproportionate impact of infection-induced SARS-CoV-2 positivity was observed across different ethnic/racial subpopulations and incomes, and differences in antibody levels across different demographics were identified. Taken together, this information may inform public health policy to protect vulnerable populations. IMPORTANCE We employed a highly innovative noninvasive multiplex oral fluid SARS-CoV-2 IgG assay to ascertain our seroprevalence estimates. This laboratory-developed test has been applied in NCI's SeroNet consortium, possesses high sensitivity and specificity according to FDA Emergency Use Authorization guidelines, correlates strongly with SARS-CoV-2 neutralizing antibody responses, and is Clinical Laboratory Improvement Amendments-approved by the Johns Hopkins Hospital Department of Pathology. It represents a broadly scalable public health tool to improve understanding of recent and past SARS-CoV-2 exposure and infection without drawing any blood. To our knowledge, this is the first application of a high-performance salivary SARS-CoV-2 IgG assay to estimate population-level seroprevalence, including identifying COVID-19 disparities. We also are the first to report differences in SARS-CoV-2 IgG responses by COVID-19 vaccine manufacturers (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]). Our findings demonstrate remarkable consistency with those of blood-based SARS-CoV-2 IgG assays in terms of differences in the magnitude of SARS-CoV-2 IgG responses between COVID-19 vaccines.

Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis.

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these combination therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that ME-344 could enhance the anti-AML activity of VEN. Here we report that ME-344 synergized with VEN to target AML cell lines and primary patient samples while sparing normal hematopoietic cells. Cooperative suppression of OXPHOS was detected in a subset of AML cell lines and primary patient samples. Metabolomics analysis revealed a significant reduction of purine biosynthesis metabolites by ME-344. Further, lometrexol, an inhibitor of purine biosynthesis, synergistically enhanced VEN-induced apoptosis in AML cell lines. Interestingly, AML cells with acquired resistance to AraC showed significantly increased purine biosynthesis metabolites and sensitivities to ME-344. Furthermore, synergy between ME-344 and VEN was preserved in these AraC-resistant AML cells. These results translated into significantly prolonged survival upon combination of ME-344 and VEN in NSGS mice bearing parental or AraC-resistant MV4-11 leukemia. This study demonstrates that ME-344 enhances VEN antileukemic activity against preclinical models of AML by suppressing OXPHOS and/or purine biosynthesis.

Novel mitochondria-targeting compounds selectively kill human leukemia cells.

Acute myeloid leukemia (AML) is a heterogeneous group of aggressive hematological malignancies commonly associated with treatment resistance, high risk of relapse, and mitochondrial dysregulation. We identified six mitochondria-affecting compounds (PS compounds) that exhibit selective cytotoxicity against AML cells in vitro. Structure-activity relationship studies identified six analogs from two original scaffolds that had over an order of magnitude difference between LD50 in AML and healthy peripheral blood mononuclear cells. Mechanistically, all hit compounds reduced ATP and selectively impaired both basal and ATP-linked oxygen consumption in leukemic cells. Compounds derived from PS127 significantly upregulated production of reactive oxygen species (ROS) in AML cells and triggered ferroptotic, necroptotic, and/or apoptotic cell death in AML cell lines and refractory/relapsed AML primary samples. These compounds exhibited synergy with several anti-leukemia agents in AML, acute lymphoblastic leukemia (ALL), or chronic myelogenous leukemia (CML). Pilot in vivo efficacy studies indicate anti-leukemic efficacy in a MOLM14/GFP/LUC xenograft model, including extended survival in mice injected with leukemic cells pre-treated with PS127B or PS127E and in mice treated with PS127E at a dose of 5 mg/kg. These compounds are promising leads for development of future combinatorial therapeutic approaches for mitochondria-driven hematologic malignancies such as AML, ALL, and CML.

Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for leukemia cell survival and demonstrate a direct relationship between NOTCH1, elevated OxPhos gene expression, and acquired chemoresistance in pre-leukemic and leukemic models. Disrupting OxPhos with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction of metabolic shut-down and redox imbalance in NOTCH1-mutated and less so in NOTCH1-wt T-ALL cells. Mechanistically, inhibition of OxPhos induces a metabolic reprogramming into glutaminolysis. We show that pharmacological blockade of OxPhos combined with inducible knock-down of glutaminase, the key glutamine enzyme, confers synthetic lethality in mice harboring NOTCH1-mutated T-ALL. We leverage on this synthetic lethal interaction to demonstrate that IACS-010759 in combination with chemotherapy containing L-asparaginase, an enzyme that uncovers the glutamine dependency of leukemic cells, causes reduced glutaminolysis and profound tumor reduction in pre-clinical models of human T-ALL. In summary, this metabolic dependency of T-ALL on OxPhos provides a rational therapeutic target.

Simulation-based ventilatory training for the caregivers at primary and rural health care workers in Central India for dealing with COVID-19 pandemic: recommendations.

In 2020 COVID-19 made a major burden on health care system. The capacity of the healthcare system particularly emergency departments, ICU, hospital beds are insufficient to manage the increasing number of patients in cities and rural areas too. The primary health care centers and rural hospitals need preparedness for such disasters conditions. Novel and future oriented solutions are needed to effectively address the unprecedented pressure on the healthcare systems created by the COVID-19 pandemic. Considering the lacunae in healthcare system at primary level, various challenges encountered during pandemic has been identified and training session in consortia with simulation based training program for the training of the doctors, nurses, attendants and other related healthcare staff of Primary Health Center and Rural Hospitals intending to prepare them for future challenges in ventilatory care of COVID-19 has been carried out. After these training session certain conclusions and recommendations were drawn which could be able our health care system to be prepared for more critical situations and we can take our primary health care system at new horizon.

Airway Blocks Vs LA Nebulization- An interventional trial for Awake Fiberoptic Bronchoscope assisted Nasotracheal Intubation in Oral Malignancies.

BACKGROUND: Patients with intra-oral malignancies warrants use of awake Fiberoptic assisted naso-thracheal intubation to secure an airway due to multiple risk factors leading to anticipated difficult airway. Different techniques such as airway blocks, local anesthesia (LA) gargles, spray, nebulization and  mild  sedation are in practice to improve  the success rate of fiberoptic assisted intubation. METHODS: Sixty patients  of  ASA I and II with Mallampatti score 3 and above, posted for Commando operations were enrolled in this study and were divided into 2 groups. Group AB (Airway Block, n=30) were given Superior laryngeal nerve block bilaterally and recurrent laryngeal nerve block  transtracheally  with Inj  2% Lignocaine. Second Group AN (Airway Nebulization, n=30)  patients airway was nebulized with 4% Lignocaine  with ultrasonic nebulizer. After confirmation of satisfactory anesthesia clinically Fiber-optic assisted naso-tracheal intubation was attempted. Hemodynamic monitoring, total time taken for intubation, patients comfort and any complications occurred were noted. Statistical Analysis- All the observed values were tabulated and analyzed using software SPSS version 17.0. RESULTS: Demography and Hemodynamic observations were comparable in the groups.  The time taken for intubation, patient comfort score, intubation conditions were excellent in AB group than in group AN. Airway complications like laryngospasm and cough were noted in AN Group. CONCLUSIONS: Judicial use of combined Airway blocks such as Bilateral Superior and trans-tracheal recurrent laryngeal nerve blocks could facilitate a successful fiber-optic assisted awake naso-tracheal intubation in anticipated difficult intubation with negligible complications.
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Evaluation of the Role of Propolis and a New Herbal Ointment in Promoting Healing of Traumatic Oral Ulcers: An Animal Experimental Study.

Most of the currently used medications for the treatment of oral ulcers focus primarily on providing symptomatic relief and preventing secondary infections. Not much attention has been paid in the past on agents that can promote healing of these lesions. In the current study, we have tested and compared the efficacy of such wound healing promoting agents i.e. Propolis (product obtained from Bees) and a newly developed herbal ointment (containing extracts of Azadirachta indica (Neem), Linum usitatissimum L.(Linseed) oil, and resin of Shorea robusta) in experimental rabbits. METHODOLOGY: Traumatic oral ulcers were inflicted in experimental rabbits (New Zealand white) with the help of a punch biopsy instrument. The animals were then divided into three groups each group consisted of 12 animals (n = 12), Group I was the untreated control group and Group II was topically treated with nonalcohol extract of propolis and Group III was treated with newly developed herbal ointment. Histological healing scores of the ulcers were evaluated on day 7 and day 14. Data were statistically analyzed using descriptive and inferential statistic methods. RESULTS: In Group III treated with newly developed herbal ointment, significantly higher healing scores, in comparison to the untreated control group (Group I) and propolis (Group II) was observed on day 7 and 14. Improved healing scores in prapolis-treated group were observed than the untreated control group. However, the difference was not statistically significant on both day 7 and day 14. CONCLUSION: With the newly developed herbal ointment, superior healing of traumatic oral ulcers was observed.

Quarantine an effective mode for control of the spread of COVID19? A review.

The outbreak of COVID- 19 disease has taken the world by surprise. The disease mainly affects the respiratory system and is caused by a strain of coronavirus named SARS-CoV-2. Due to its high recombination rates the virus has an immense potential to spread rapidly. Within months of the first case being reported in Wuhan China, the disease has turned rapidly into a pandemic. The world health experts are already actively looking for a definite cure or vaccine for the disease, but till that many of the countries across the globe are looking up onto mass quarantine measures as a method to control its spread. This article is an attempt to review the effectiveness of these measures and the possible adverse effects of the same. Other possible modes of prevention and controlling the spread of the disease have also been reviewed in the article.

Oral mucosal changes in pemphigus vulgaris and its treatment: A case report.

Pemphigus Vulgaris is an autoimmune disease that causes severe blistering of the skin and mucous membrane which are fragile and breaks away leaving erosions that are extremely painful. Here we report a case of a patient suffering from pemphigus vulgaris with typical oral manifestations. We have reported the effect of treatment after two consecutive recalls at an interval of 1 week where the patient got 100% relief from her previous signs and symptoms.

Stability Indicating Reverse Phase HPLC Method for Estimation of Rifampicin and Piperine in Pharmaceutical Dosage Form.

BACKGROUND: High performance liquid chromatography is an integral analytical tool in assessing drug product stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants that can form on storage or manufacturing, plus detect any drug-related impurities that may be introduced during synthesis. OBJECTIVE: A simple, economic, selective, precise, and stability-indicating HPLC method has been developed and validated for analysis of Rifampicin (RIFA) and Piperine (PIPE) in bulk drug and in the formulation. METHOD: Reversed-phase chromatography was performed on a C18 column with Buffer (Potassium Dihydrogen Orthophosphate) pH 6.5 and Acetonitrile, 30:70), (%, v/v), as mobile phase at a flow rate of 1 mL min-1. RESULT: The detection was performed at 341 nm and sharp peaks were obtained for RIFA and PIPE at retention time of 3.3 ± 0.01 min and 5.9 ± 0.01 min, respectively. The detection limits were found to be 2.385 ng/ml and 0.107 ng/ml and quantification limits were found to be 7.228ng/ml and 0.325ng/ml for RIFA and PIPE, respectively. The method was validated for accuracy, precision, reproducibility, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines. CONCLUSION: Stress study was performed on RIFA and PIPE and it was found that these degraded sufficiently in all applied chemical and physical conditions. Thus, the developed RP-HPLC method was found to be suitable for the determination of both the drugs in bulk as well as stability samples of capsule containing various excipients.

Omega-3 Fatty Acid Grafted PAMAM-Paclitaxel Conjugate Exhibits Enhanced Anticancer Activity in Upper Gastrointestinal Cancer Cells.

Upper Gastrointestinal Cancers (UGCs) are a leading cause of cancer-related deaths worldwide. Paclitaxel (PTX) is frequently used for the treatment of UGCs; however, low bioavailability, reduced solubility, and dose-dependent toxicity impede its therapeutic use. PAMAMG4.0 -NH2 -DHA is synthesized by linking amine-terminated fourth-generation poly(amidoamine) (PAMAMG4.0 -NH2 ) dendrimers with omega-3 fatty acid docosahexaenoic acid (DHA). Next, PAMAMG4.0 -NH2 -DHA-PTX (DHATX) and PAMAMG4.0 -NH2 -PTX (PAX) conjugates are synthesized by subsequent covalent binding of PTX with PAMAMG4.0 -NH2 -DHA and PAMAMG4.0 -NH2 , respectively. 1 H-NMR and MALDI-TOF analyses are performed to confirm conjugation of DHA to PAMAMG4.0 -NH2 and PTX to PAMAMG4.0 -NH2 -DHA. The cell viability, clonogenic cell survival, and flow cytometry analyses are used to determine the anticancer activity of PTX, PAX, and DHATX in UGC cell lines. The in vitro data indicate that treatment with DHATX is significantly more potent than PTX or PAX at inhibiting cellular proliferation, suppressing long-term survival, and inducing cell death in UGC cells.

Review of pulmonary adverse effects of infliximab therapy in Crohn's disease.

INTRODUCTION: Anti-inflammatory therapies are the mainstay for the treatment of inflammatory bowel disease (IBD) in children and adults, including biologics such as infliximab. While there is extensive literature on the general side effects of therapy with infliximab, the data on pulmonary adverse effects remains sparse. This article summarizes the literature related to pulmonary adverse effects of Infliximab therapy in Crohn's Disease. AREA COVERED: Published reports of specific pulmonary complications during ongoing therapy with infliximab in patients with IBD were included in the review. A wide variety of infectious and non-infectious complications have been reported with the use of infliximab therapy in IBD. EXPERT OPINION: It is important to carefully evaluate respiratory signs and symptoms in patients with IBD, especially those receiving biologic therapies. Besides infectious complications, other non-infectious pulmonary adverse effects associated with the use of infliximab should be considered in patients with IBD. Further, it is important to differentiate primary pulmonary involvement of IBD from pulmonary adverse effects of infliximab therapy. An algorithm for assessing patients with IBD presenting with pulmonary symptoms is provided as a guide for clinicians for medical decision-making.

Cost-effectiveness of noninvasive ventilation for chronic obstructive pulmonary disease-related respiratory failure in Indian hospitals without ICU facilities.

INTRODUCTION: The majority of Indian hospitals do not provide intensive care unit (ICU) care or ward-based noninvasive positive pressure ventilation (NIV). Because no mechanical ventilation or NIV is available in these hospitals, the majority of patients suffering from respiratory failure die. OBJECTIVE: To perform a cost-effective analysis of two strategies (ward-based NIV with concurrent standard treatment vs standard treatment alone) in chronic obstructive pulmonary disease (COPD) respiratory failure patients treated in Indian hospitals without ICU care. MATERIALS AND METHODS: A decision-analytical model was created to compare the cost-effectiveness for the two strategies. Estimates from the literature were used for parameters in the model. Future costs were discounted at 3%. All costs were reported in USD (2012). One-way, two-way, and probabilistic sensitivity analysis were performed. The time horizon was lifetime and perspective was societal. RESULTS: The NIV strategy resulted in 17.7% more survival and was slightly more costly (increased cost of $101 (USD 2012) but resulted in increased quality-adjusted life-years (QALYs) (1.67 QALY). The cost-effectiveness (2012 USD)/QALY in the standard and NIV groups was $78/QALY ($535.02/6.82) and $75/QALY ($636.33/8.49), respectively. Incremental cost-effectiveness ratio (ICER) was only $61 USD/QALY. This was substantially lower than the gross domestic product (GDP) per capita for India (1489 USD), suggesting the NIV strategy was very cost effective. Using a 5% discount rate resulted in only minimally different results. Probabilistic analysis suggests that NIV strategy was preferred 100% of the time when willingness to pay was >$250 2012 USD. CONCLUSION: Ward-based NIV treatment is cost-effective in India, and may increase survival of patients with COPD respiratory failure when ICU is not available.