The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: A phase I trial.

Minnelide is a water-soluble disodium salt variant of triptolide, an HSP70 inhibitor that can prevent tumor progression and induce apoptosis. Maximum tolerated dose (MTD), safety, and antitumor activity of Minnelide alone and its combination with paclitaxel were evaluated in this open-label, single-center, dose-escalation phase I study (NCT05566834) in patients who were previously treated for advanced gastric cancer (AGC). Minnelide was administered orally using a 3 + 3 dose-escalation design as monotherapy (Regimen A), and in combination with paclitaxel (Regimen B & C). Our results show that no patients experienced dose limiting toxicity (DLT) in the combination group (Regimen B& C) while 2 patients experienced DLT from the Regimen A group (n = 11) (Minnelide 1.5 mg). The MTD was Minnelide 1.25 mg once daily for 21days Q4 weeks as monotherapy. The most common Grade ≥3 AEs were neutropenia (19.4 %) and abdominal pain (11.1 %). In Regimen C, 71.5 % achieved either a partial response or a stable disease with the median PFS of 4.5 months, and the median OS of 10.7 months. The combination of Minnelide plus paclitaxel as salvage treatment in AGC patients showed meaningful clinical activity with a manageable safety profile. Based on these encouraging results, a phase II study is being initiated to test the effectiveness of the combination regimen in patients with advanced gastric cancer.

Development of alkali activated paver blocks for medium traffic conditions using industrial wastes and prediction of compressive strength using random forest algorithm.

Geopolymer is an environment friendly construction material that could be synthesized using either the natural source or the industrial byproducts such as flyash and GGBS. The characteristics of the Geopolymer rely on the proportion of the flyash and GGBS and the concentration of the activator solution used. In this research work, the effect of partial replacement of flyash with GGBS in proportions such as 0, 10, 20, 30 and 40% is investigated. Also Molarity of NaOH are tested from 8 to 14 M and both the parameters are optimized. In this optimized Geopolymer concrete, the utilization of iron slag as a partial substitute for river sand in various proportions such as 10, 15, 20, 25, 30 35, 40 and 45% are investigated. The optimized Geopolymer concrete with iron slag is investigated for its performance as a paver block with incorporation of banana fiber in proportions such as 0, 0.5, 1 and 1.5 and is compared with conventional cement concrete paver block. The results show that there is a significant enhancement in the properties of Geopolymer concrete with the different levels of optimization and the utilization of natural banana fiber. The developed sustainable paver block was found to with stand medium traffic conditions as per IS 15658:2006. Further this study employed random forest (RF) algorithm for the prediction of compressive strength of geopolymer concrete specimens for the variable parameters such as molarity of alkaline solution, Flyash/GGBS ratio and partial replacement of river sand with iron slag. The performance evaluation parameters represented high accuracy of developed RF model. This research work unleashes a heft potential of Geopolymer concrete to develop economical eco-friendly sustainable paver blocks to the society through mitigation of environmental strain on the ecosystem.

Covid-19 cure perceptions and media use in India.

BACKGROUND: During the early phases of Covid-19, social media platforms became a significant source of misinformation, and India emerged as a global hotspot. Studies show that 'miracle cure' for preventing and treating Covid-19 infection has been a prominent topic of misinformation. This study explores the extent to which beliefs in cure for Covid-19 in three prominent medical traditions popular in India are associated with the exposure to and trust in various sources from which the public access information. METHODS: We conducted an online structured questionnaire survey of 500 respondents in August 2020 in four major cities of India. RESULTS: Despite the scientific consensus at that time that there was no cure for Covid-19, close to three-quarters of our respondents believe that there was a cure in at least one of the three popular medical traditions in India: Allopathy, Homeopathy, and Ayurveda. We find that exposure to and trust in WhatsApp are associated with false beliefs regarding the existence of a cure for Covid-19 (p = 0.001 and p = 0.014, respectively). While trust in science is associated with correct beliefs (p = 0.025), there is evidence that trust in government information may foster incorrect beliefs (p = 0.031). CONCLUSIONS: The high trust in scientific research and its potential ability to instill correct beliefs could be exploited to combat Covid-19 misinformation in India. Potential interventions such as awareness campaigns to increase digital media literacy, regulating social media platforms, and voluntary content regulation by social media platforms - might help policymakers tackle Covid-19 related misinformation effectively.

Salvage of Hindfoot Charcot with Osteomyelitis and Ulceration: A Case Report.

Diabetic Charcot arthropathy of the ankle, due to the presence of multiplanar deformities, and associated medical comorbidities, poses a challenge for treating physicians. The situation becomes more complicated when accompanied by ulceration and osteomyelitis, leaving limited salvage options. We present a case of advanced Charcot ankle arthropathy with osteomyelitis and ulcerated hindfoot. It was managed by talectomy and antibiotic-impregnated cement beads, followed by hindfoot arthrodesis using a retrograde intramedullary nail six weeks later. This two-stage reconstruction approach resulted in an ulcer-free, stable, plantigrade foot at one-year postoperative follow-up.

A Smart Solution for Cancer Patient Monitoring Based on Internet of Medical Things Using Machine Learning Approach.

The Internet of Medical Things (IoMT) is a huge, exciting new phenomenon that is changing the world of technology and innovating various industries, including healthcare. It has specific applications and changes in the medical world based on what can be done for clinical workflow models. The first and most fundamental thing that IoMT does in healthcare is to bring a flood of new data into medical processes. In this study, an efficient Internet of Medical Things based cancer detection model was proposed. In fact, for many, new fitness monitors and watches are one of the best examples on the Internet; these mobile, portable, wearable devices can record real-time heart rate, blood pressure, and eye movement of cancer patients. These details are sent to doctors or anywhere else. The proposed method leads to a kind of big data renaissance in the health service. The proposed model gets more accuracy while comparing with the existing models. This will help the doctors to analyze the patients' health report and provides better treatment.

Olecranon Fracture in an Older Adult Treated With Locking Plate Osteosynthesis.

Although olecranon fractures are not uncommon in the geriatric population, there has been a considerable difference of opinion between surgical and nonsurgical treatments. Surgical treatment is usually deferred in the elderly, even for displaced olecranon fractures, because of inherent risks associated with poor bone quality and soft tissues, which often necessitate further surgeries. However, nonoperative treatment frequently results in an inability to regain full extension strength of the elbow, which can be disabling in select older adults with higher functional demands. We present an active older adult with a displaced olecranon fracture, who achieved a satisfactory result after open reduction and internal fixation (ORIF) using a low-profile locking plate.

The Effect of Minnelide against SARS-CoV-2 in a Murine Model

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of coronavirus disease 2019, COVID-19, and the current COVID-19 pandemic. Even as more vaccine candidates are released, more treatment options are critically needed. Here, we investigated the use of Minnelide, a water soluble pro-drug with anti-inflammatory properties, for the treatment of COVID-19. To do this, k18-hACE2 mice were infected with SARS-CoV-2 or given PBS control intranasally. The next day mice were either treated daily with low dose (0.0025mg/day) or high dose Minnelide (0.005mg/day), or given vehicle control intraperitoneal. Mice were weighed daily, and sacrificed at day 6 and 10 post-infection to analyze viral burden, cytokine response, and pathology. We observed a reduction in viral load in the lungs of Minnelide-treated mice infected with SARS-CoV-2 at day 10 post-infection compared to day 6 post-infection. All SARS-CoV-2 infected non-treated mice were moribund six days post-infection while treatment with Minnelide extended survival for both low (60% survival) and high (100% survival) dose treated mice ten days post-infection. Interestingly, cytokine analysis demonstrated a significant reduction in IL-6 (lung and heart) and D-dimer (serum) in high dose treated SARS-CoV-2 infected mice compared to mice infected with SARS-CoV-2 alone at day 6 post-infection. Additionally, histology analysis revealed that Minnelide treatment significantly improved lung pathology ten days post-infection with SARS-CoV-2 with all the mice exhibiting normal lung tissue with thin alveolar septa and no inflammatory cells. Overall, our study exhibits potential for the use of Minnelide to improve survival in COVID-19 patients.

LncRNA MEG3 promotes proliferation and differentiation of osteoblasts through Wnt/ß-catenin signaling pathway.

OBJECTIVE: We aimed at detecting the expression of long non-coding ribonucleic acid (lncRNA) maternally expressed 3 (MEG3) in the serum of fracture patients, and at investigating its impacts on the proliferation and differentiation of osteoblasts and the specific molecular mechanism of action. PATIENTS AND METHODS: The serum samples of 48 fracture patients diagnosed in our hospital (Fracture group) and 30 healthy people receiving physical examination (Health group) were collected. The expression level of serum lncRNA MEG3 in Fracture group and Health group was measured via reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, a small interfering RNA (siRNA) was applied to construct mouse osteoblast cell line MC3T3-E1 with a stable knockout of MEG3. The growth status of the cell was observed, and the impacts of MEG3 knockout on the osteoblast proliferation were determined using cell counting kit-8 (CCK-8), a proliferation activity detection kit. Meanwhile, 5-ethynyl-2'-deoxyuridine (EdU) staining was applied to detect the proportion of EdU positive cells in the osteoblasts in Control group and MEG3 knockout group (MEG3 siRNA group). In addition, RT-PCR was performed to measure the messenger RNA (mRNA) levels of differentiation-related genes. Finally, RT-PCR and Western blotting assay were adopted to analyze the expression of the Wnt/ß-catenin signaling pathway. RESULTS: The expression of serum lncRNA MEG3 in fracture patients was increased markedly (p<0.05). Results of in-vitro cell experiment indicated that intervention with MEG3 siRNA could obviously promote the proliferation and differentiation of osteoblast cell line MC3T3-E1. The results of RT-PCR and Western blotting assay revealed that the role of MEG3 in promoting differentiation and proliferation might be mediated by the activation of the Wnt/ß-catenin signaling pathway in osteoblasts. CONCLUSIONS: LncRNA MEG3 can promote the proliferation and differentiation of osteoblasts by activating the Wnt/ß-catenin signaling pathway, so it is expected to become a new target for accelerating the fracture healing.

Rare complication of appendix: small bowel gangrene caused by the appendicular knot.

Intestinal knot formation was first described by Riverius in 16th century and later by Rokitansky in 1836. We report a very rare cause of small bowel gangrene caused by appendiceal knotting on to the ileum in a previously healthy mid aged lady. Patient underwent laparatomy and right hemicolectomy and primary anastomosis. The intra operative findings were the appendix was twisting (knotting) the small bowel about 40cm from the terminal ileum and causing gangrene to the segment of small bowel. Appendicitis is a common condition and management is usually straightforward. However we must be aware of rare complications which may arise that require a change from the standard treatment of acute appendicitis.

Teratomas in central nervous system: a clinico-morphological study with review of literature.

BACKGROUND: Cranio-spinal axis teratomas are rare. This subset is interesting because symptoms can be varied, depending on the location. Histopathology is diagnostic; most of the lesions are benign. Rarely, malignancy develops in any of the somatic components. AIMS: To study the demographic, clinico-morphological and follow-up data of central nervous system (CNS) teratomas. MATERIALS AND METHODS: Cases diagnosed as mature or immature teratomas in the CNS over a 20-year period were included in the study. Clinico-radiological, demographic and follow-up data of these cases were analyzed. RESULTS: A total of 14 tumors were diagnosed as teratomas. Of these, 11 were mature cystic teratomas; and 1 case each, of teratoma with malignant transformation, terato-carcinoma and mixed germ cell tumor (immature teratoma with germinoma). Six of the 14 cases were intracranial and 8 were spinal. Presenting features varied according to the location. Radiologically, contrast enhancement with predominantly solid component was suggestive of malignancy or an aggressive tumor. Morphologically, a variety of tissue derivatives were seen in the cases. Excision was curative or provided symptomatic relief in most cases; terato-carcinoma and mixed germ cell tumor patients needed adjuvant radiotherapy. CONCLUSION: CNS teratomas are rare. Morphology and location decide outcome.

Pro-environmental behavior: rational choice meets moral motivation.

The determinants of individual behaviors that provide shared environmental benefits are a longstanding theme in social science research. Alternative behavioral models yield markedly different predictions and policy recommendations. This paper reviews and compares the literatures from two disciplines that appear to be moving toward a degree of convergence. In social psychology, moral theories of pro-environmental behavior have focused on the influence of personal moral norms while recognizing that external factors, such as costs and incentives, ultimately limit the strength of the norm-behavior relationship. Rational choice models, such as the theory of planned behavior in social psychology and the theories of voluntary provision of public goods in economics, have sought to incorporate the effects of personal norms and to measure their importance in explaining behaviors, such as recycling and the demand for green products. This paper explores the relationship between these approaches and their implications for the theory and practice of ecological economics.

Superfund, hedonics, and the scales of environmental justice.

Environmental justice (EJ) is prominent in environmental policy, yet EJ research is plagued by debates over methodological procedures. A well-established economic approach, the hedonic price method, can offer guidance on one contentious aspect of EJ research: the choice of the spatial unit of analysis. Environmental managers charged with preventing or remedying inequities grapple with these framing problems. This article reviews the theoretical and empirical literature on unit choice in EJ, as well as research employing hedonic pricing to assess the spatial extent of hazardous waste site impacts. The insights from hedonics are demonstrated in a series of EJ analyses for a national inventory of Superfund sites. First, as evidence of injustice exhibits substantial sensitivity to the choice of spatial unit, hedonics suggests some units conform better to Superfund impacts than others. Second, hedonic estimates for a particular site can inform the design of appropriate tests of environmental inequity for that site. Implications for policymakers and practitioners of EJ analyses are discussed.