Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses.

mRNA vaccines have emerged as an optimistic technological platform for vaccine innovation in this new scientific era. mRNA vaccines have dramatically altered the domain of vaccinology by offering a versatile and rapid approach to combating infectious diseases and virus-induced cancers. Clinical trials have demonstrated efficacy rates of 94-95% in preventing COVID-19, and mRNA vaccines have been increasingly recognized as a powerful vaccine platform. Although mRNA vaccines have played an essential role in the COVID-19 pandemic, they still have several limitations; their instability and degradation affect their storage, delivery, and over-all efficiency. mRNA is typically enclosed in a transport mechanism to facilitate its entry into the target cell because it is an unstable and negatively charged molecule. For instance, mRNA that is given using lipid-nanoparticle-based vaccine delivery systems (LNPs) solely enters cells through endocytosis, establishing an endosome without damaging the cell membrane. The COVID-19 pandemic has accelerated the development of mRNA vaccine platforms used to treat and prevent several infectious diseases. This technology has the potential to change the future course of the disease by providing a safe and effective way to combat infectious diseases and cancer. A single-stranded genetic sequence found in mRNA vaccines instructs host cells to produce proteins inside ribosomes to elicit immunological responses and prepare the immune system to fight infections or cancer cells. The potential applications of mRNA vaccine technology are vast and can lead to the development of a preferred vaccine pattern. As a result, a new generation of vaccinations has gradually gained popularity and access to the general population. To adapt the design of an antigen, and even combine sequences from different variations in response to new changes in the viral genome, mRNA vaccines may be used. Current mRNA vaccines provide adequate safety and protection, but the duration of that protection can only be determined if further clinical research is conducted.

Current approaches in smart nano-inspired drug delivery: A narrative review.

Background and Aim: The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side-effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off-target side-effects. Methods: A literature search was done to collate papers and reports about the currently available various strategies for smart nano-inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Results: Smart drug delivery is a cutting-edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side-effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Conclusion: Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine.

Cystocerebral Syndrome in a Patient with Altered Mental Status.

BACKGROUND Cystocerebral syndrome is delirium occurring in the elderly that results from urinary retention and acute bladder distension. Urinary retention can cause cerebral issues, such as altered mental status, without having an infection present. The pathophysiology is possibly due to increased catecholamine secretion while attempting to micturate. Due to its presenting symptoms, most physicians begin cerebrovascular workup, performing unnecessary and, often, invasive imaging studies. Although easily overlooked as a differential diagnosis, cystocerebral syndrome is an easily treatable cause of delirium and should be considered during treatment of elderly patients with delirium. CASE REPORT The patient was an 89-year-old man with a medical history of chronic obstructive airway disease, dementia, hypertensive disorder, and gastroesophageal reflux disease who presented with altered mental status secondary to urinary incontinence. The computed tomography scan without contrast showed a large volume of impacted stool in the cecum, with a distended urinary bladder. This case report describes his presentation, medical treatment, and outcome and discusses areas of gap improvement. CONCLUSIONS To date, there are only a handful of published articles on cystocerebral syndrome. This case report aims to add the awareness of bladder distention as an etiology of cystocerebral syndrome to the body of knowledge in the scientific community in the hope that patients will be identified and treated earlier, more safely, and at a reduced cost. Cystocerebral syndrome needs to be extensively addressed in research, and physicians should consider it one of the important differential diagnoses of delirium among elderly men.

Improving case duration accuracy of orthopedic surgery using bidirectional encoder representations from Transformers (BERT) on Radiology Reports.

PURPOSE: A major source of inefficiency in the operating room is the mismatch between scheduled versus actual surgical time. The purpose of this study was to demonstrate a proof-of-concept study for predicting case duration by applying natural language processing (NLP) and machine learning that interpret radiology reports for patients undergoing radius fracture repair. METHODS: Logistic regression, random forest, and feedforward neural networks were tested without NLP and with bag-of-words. Another NLP method tested used feedforward neural networks and Bidirectional Encoder Representations from Transformers specifically pre-trained on clinical notes (ClinicalBERT). A total of 201 cases were included. The data were split into 70% training and 30% test sets. The average root mean squared error (RMSE) were calculated (and 95% confidence interval [CI]) from 10-fold cross-validation on the training set. The models were then tested on the test set to determine proportion of times surgical cases would have scheduled accurately if ClinicalBERT was implemented versus historic averages. RESULTS: The average RMSE was lowest using feedforward neural networks using outputs from ClinicalBERT (25.6 min, 95% CI: 21.5-29.7), which was significantly (P < 0.001) lower than the baseline model (39.3 min, 95% CI: 30.9-47.7). Using the feedforward neural network and ClinicalBERT on the test set, the percentage of accurately predicted cases, which was defined by the actual surgical duration within 15% of the predicted surgical duration, increased from 26.8 to 58.9% (P < 0.001). CONCLUSION: This proof-of-concept study demonstrated the successful application of NLP and machine leaning to extract features from unstructured clinical data resulting in improved prediction accuracy for surgical case duration.

An extremely rare case of feeding jejunostomy proceeding to intussusception.

Key Clinical Message: Feeding jejunostomy (FJ) is one of the frequently performed surgical procedures for enteral nutrition, but intussusception a very rare complication with quite challenging clinical outcome. It symbolizes a surgical emergency requiring prompt diagnosis. Abstract: Feeding jejunostomy (FJ) is a minor surgical intervention, which might lead to consequences that are potentially fatal. Mechanical issues such as infection, tube dislocation or migration, electrolyte and fluid imbalances, as well as complaints of gastrointestinal tract, are the most frequent consequences. A 76-year-old female, who is a known case of carcinoma (CA) esophagus: Stage 4 with Eastern Cooperative Oncology Group (ECOG) Class 3 presented with complaints of difficulty in swallowing and vomiting. As a part of palliative treatment, FJ is done and patient was discharged on postoperative day (POD) 2. Patient again presented to emergency department after 2 months with complaints of pain abdomen, unable to pass flatus and stools for 2 days. Contrast-enhanced computed tomography was done, which revealed intussusception of jejunum with lead point as tip of feeding tube. Intussusception of jejunal loops is noted 20 centimeters distal to the site of insertion of FJ tube with tip of feeding tube as lead point. Reduction of bowel loops was achieved by gentle compression of distal part and are found to be viable. FJ tube was then removed and repositioned after which the obstruction got relieved. Intussusception is an extremely rare complication of FJ, where the clinical presentation can be likely to the various causes of small bowel obstruction. The fatal complications like intussusception in FJ can be prevented by remembering some technical considerations, such as attaching a 4-5 cm segment of the jejunum to the abdominal wall rather than a single-point fixation and maintaining a minimum distance of 15 cm between the duodenojejunal (DJ) flexure and the FJ site.

Face Transplantation: What You Need to Know?

Since the 1990s, face transplants have gotten a lot of press and public attention across the world. After a transplant was disclosed in November 2005, the first recipient, Isabelle Dinoire, found herself at the center of a spectacular event of surgical innovation. Up till August 2020, 47 transplants have been performed globally (including two retransplants), all of which have received substantial media attention. Hundreds of publications addressing the procedure's medicinal, physical, psychological, and ethical ramifications have been published in the scholarly literature, far outnumbering the procedure's occurrence. Face transplants have also appeared in films, television shows, and novels, indicating a desire to explore the social and interpersonal consequences of face variance. This is an attempt to present a comprehensive context of face transplantation progress and practice, based mostly on extant documentary sources. It traces the history of face transplants, identifying major milestones and themes along the way and focusing on its development as a therapeutic option for individuals with severe facial abnormalities. There are still important questions to be asked about the patient's perspective, as well as the complex philosophical and sociological meanings of the face, but this article focuses on the institutional and cultural factors that have allowed for such an ethically complex and radical surgery to take place. Opportunity and financial feasibility are among them, as are expertise, ambition, and an awareness of patient needs.

Caffeine: What Is Its Role in Pain Medicine?

Caffeine is the world's most widely used psychoactive legal substance. The involvement of caffeine in pain management has gotten minimal attention in the past, but it is getting more attention now. This article provides a brief assessment of the literature to clarify the role of caffeine as a pain reliever and stimulate the interest of researchers. Caffeine affects adenosine receptors, which are involved in nociception, and plays a significant role in pain regulation. Caffeine's usage as an adjuvant therapy has been extensively documented in the literature, and it is now accessible in certain over-the-counter drugs. The mixture of coffee and morphine for pain reduction in individuals with terminal cancer has shown mixed outcomes in studies. Caffeine can be utilized for hypnic headaches and post-dural puncture headaches since it is crucial in pain regulation. Caffeine has the potential to help in pain management. Caffeine's usage for migraines and end-stage cancer disease is not well acknowledged. Further research is essential to focus on caffeine's potential role in various forms of pain, including dosage escalation and outcome assessment standardization.

Association of IL1R1 gene (SNP rs2071374) with the risk of preeclampsia.

BACKGROUND: Association of IL1R1rs2071374 with the risk of preeclampsia compared with normotensive pregnant women. METHODOLOGY: The study was a case-control study with 304 pregnant women comprising of preeclampsia (n = 152) and normotensive pregnancies (n = 152). And SNP rs2071374 was genotyped by PCR-RFLP method. RESULTS: The presence of IL1R1rs2071374G allele was associated with the increased risk of preeclampsia P = 0.01741, odds ratio = 0.7006 (95% CI: 0.5023-0.9759). CONCLUSION: The results indicated that there was an association in IL1R1 rs2071374SNP with preeclampsia compared to non-preeclampsia women. It is the first study to evaluate that IL1R1 polymorphism is correlated with preeclampsia pathogenesis in the Population in India.

Drug-Associated Eosinophilic Fasciitis: A Case of Eosinophilic Fasciitis Secondary to Cemiplimab Therapy.

BACKGROUND Eosinophilic fasciitis, also known as Shulman syndrome, is a rare inflammatory condition characterized by diffuse erythema and progressive collagenous thickening of the subcutaneous fascia. The underlying cause remains to be definitively established; however, several drugs have been linked to this uncommon clinical entity. We present a rare case of eosinophilic fasciitis secondary to immune checkpoint inhibitor therapy. CASE REPORT A 72-year-old woman with metastatic cutaneous squamous cell carcinoma presented to the rheumatology clinic for evaluation of joint pain that developed 3 weeks after beginning treatment with cemiplimab. The correlation of clinical history and physical examination was most consistent with osteoarthritis. Symptoms improved after a short course of low-dose prednisone. The patient continued cemiplimab therapy for approximately 1 year and was subsequently transitioned to carboplatin and radiation therapy. However, relapse occurred shortly thereafter, and cemiplimab was restarted. Two weeks later, the patient developed severe joint pain, morning stiffness, and extensive cutaneous discoloration and induration. A skin biopsy was performed. Microscopic examination of a tissue sample showed a mononuclear infiltrate with plasma cells and eosinophils. A diagnosis of eosinophilic fasciitis was established. Cemiplimab was held and the patient was treated with hydroxychloroquine, prednisone, and sulfasalazine. Symptoms improved within 1 week. CONCLUSIONS Eosinophilic fasciitis is a rare but important adverse effect of immune checkpoint inhibitors. Individuals receiving immunotherapy should be monitored closely for symptoms of eosinophilic fasciitis, as prompt treatment is essential to prevent long-term complications.

An Atypical Presentation of Polyarteritis Nodosa: Case Report and Review of the Literature.

Polyarteritis nodosa (PAN) is a rare multisystem vasculopathy that predominantly affects medium-sized arteries. Involvement of the cardiac and/or pulmonary vasculature may be fatal. We describe a 67-year-old Japanese male who presented with multiple coronary artery aneurysms and subsequently developed lower extremity gangrene. A diagnosis of PAN was established based on the correlation of clinical presentation and laboratory and imaging findings. In addition, we review other manifestations of PAN and differential considerations for this rare but potentially lethal condition.

Atorvastatin-Induced Necrotizing Myopathy and its Response to Combination Therapy.

Atorvastatin is the most commonly used statin medication to decrease cholesterol levels and prevent atherosclerosis. Myopathy is a reported side effect of atorvastatin which can happen even after more than six months after starting the medication. The side effect on the muscle tissue can range from simple reversible myalgia to respiratory muscle compromise. Here we present a 46-year-old male who presented with myopathy after taking atorvastatin for two years. Biopsy proved immune-mediated necrotizing myopathy which responded to a combination of Rituximab and intravenous immunoglobulin therapy.

Sociodemographic Predictors of Outcomes in COVID-19: Examining the Impact of Ethnic Disparities in Northern Nevada.

Background  On March 11, 2020, the World Health Organization declared coronavirus disease-19 (COVID-19) a pandemic. Nearly five million individuals have since been diagnosed with this increasingly common and potentially lethal viral infection. Emerging evidence suggests a disproportionate burden of illness and death among minority communities. We aimed to evaluate the effect of ethnicity on outcomes among patients diagnosed with COVID-19 in Northern Nevada. Methods  The electronic health records of 172 patients diagnosed with COVID-19 were obtained from a 946-bed tertiary referral center serving Northern Nevada. Demographic and clinical characteristics were compared by ethnic group (Hispanic versus non-Hispanic). Logistic regression was used to determine predictors of mortality.  Results  Among 172 patients who were diagnosed with COVID-19 between March 12 and May 8, 2020, 87 (50.6%) identified as Hispanic and 81 (47.1%) as non-Hispanic. Hispanic individuals were significantly more likely to be uninsured and to live in low-income communities as compared to their non-Hispanic counterparts (27.6% versus 8.2% and 52.9% versus 30.6%, respectively). Hispanic patients were also less likely than non-Hispanics to have a primary care provider (42.5% versus 61.2%). However, mortality was significantly higher among the non-Hispanic population (15.3% versus 5.8%).  Conclusion  The COVID-19 pandemic has disproportionately affected Hispanic individuals in Northern Nevada, who account for only 25.7% of the population but over half of the confirmed cases. The underlying causes of ethnic disparities in COVID-19 incidence remain to be established, but further investigation may lead to more effective community- and systems-based interventions.

Double Down on Double Vision: An Unusual Case of Painful Diplopia.

Tolosa-Hunt syndrome (THS) is a rare neuro-immunological disorder characterized by severe periorbital headaches and ophthalmoplegia. In some patients, THS may occur in parallel with other autoimmune disorders. The underlying etiology of THS remains to be definitively established. However, inflammation of the cavernous sinus or orbital apex represents a hallmark feature; magnetic resonance imaging, therefore, plays a key role in establishing a diagnosis. We describe a patient who presented with concomitant THS and granulomatosis with polyangiitis. In addition, we describe the clinical and imaging findings of THS and review treatment options for this rare condition.

Large vessel stroke and COVID-19: Case report and literature review.

The clinical signs of coronavirus disease-19 (COVID-19) can be heterogenous because of the diversity of potential organ involvement. We describe a 58-year-old woman who developed new-onset dysarthria and hemiplegia and was found to be COVID-19-positive. This is among the first cases of COVID-19 presenting solely with focal neurologic deficits.