Advanced Concepts in Medicine and Medical Research Vol. 12

Introduction: Chlorophenoxy herbicides are class of synthetic herbicides used to control broad leaved weeds. Their poisoning is very rare and l has no antidote. The mission of this case report is to emphasize the role of accurate diagnosis and management of 2, 4-D herbicide intoxication.

Case Report: We report a case of 19 year old male admitted after 6h of the deliberate ingestion of the contents of a half bottle (300 ml) of weedkiller named Dallas contents. Soon after ingestion the patient gave history of vomiting, after which patient became unconscious.

Patient was unresponsive to deep painful stimulus. He was sweating profusely with a temperature of 39 degree Celsius. Patient was electively intubated for airway protection.

Patient’s metabolic acidosis also worsened. Patient’s output dropped to 5-10 ml/hr. Patient was then taken on Haemodialysis. Patient’s urine output improved and GCS also improved.

Conclusion: 2,4-Dimethylamine intoxication is uncommon, doesn’t have an antidote with very high morbidity and mortality. Other therapies, such as gastrointestinal decontamination, first emergency resuscitation, and supportive treatment with haemodialysis when needed, must be added to alkaline diuresis, which is a life-saving treatment.

Hyperlipidemia is one of the major risk factors of cardiovascular complication in diabetes. A study was undertaken to evaluate the antihyperlipidemic activity of tetrahydrocurcumin (THC). Curcuma longa (Zingiberaceae) is commonly used in the treatment of diabetes by ayurvedic physicians. Curcumin is a biologically active component isolated from the rhizome of Curcuma longa that possess antidiabetic and has been proven scientifically for high antioxidant activity and anticancer properties. THC is one of the major colorless metabolite of curcumin. THC has been reported to exhibit the same physiological and pharmacological properties of curcumin. Curcumin is rapidly metabolized during absorption from the intestine, yielding THC, which has shown the strongest antioxidant activity among all curcuminoids. The levels of total cholesterol, triglycerides, free fatty acids, phospholipids, LDL-cholesterol, VLDL-cholesterol and HMG-CoA reductase activity were significantly increased whereas the level of HDL-cholesterol was significantly decreased in serum, liver and kidney of STZ and nicotinamide induced diabetic rats. In STZ diabetic rats treated with THC and curcumin, the levels of lipids and HMG-CoA reductase activity were significantly decreased while the level of HDL-cholesterol was significantly increased. It was observed that antihyperlipidemic effect may be due to improvement in glycaemic control and increased plasma insulin activity, which may result in STZ and nicotinamide induced diabetic rats treated with THC and curcumin to maintain serum and tissue lipids in normal level. The THC administration showed more effective than curcumin. Fatty acids composition of total lipids was significantly altered in liver, kidney and brain of STZ and nicotinamide induced diabetic rats. There was an increase in the levels of palmitic acid and stearic acid with significant decrease in the levels of linolenic acid and arachidonic acid were observed in the tissue of diabetic rats. These polyunsaturated fatty acids are the major targets for reactive oxygen species (ROS) damage. This study showed that administration of THC and curcumin resulted in a significant protection against the changes in the fatty acid composition in STZ and nicotinamide induced diabetic rats.

Subacromial Impingement Syndrome (SAIS) indicates a wide range of pathology varying from subacromial bursitis to rotator cuff wear and tear. It is one of the commonest causes of 45 to 65 % of the shoulder pain syndromes, still many times it is misdiagnosed as frozen shoulder as some of its symptoms overlap. It occurs mainly due to impingement of the structures beneath the acromion process due to narrowing of the subacromial space. The narrowing can occur due to extrinsic compression or intrinsic compression. Abnormal biomechanics which includes tight pectoralis major and minor, weak scapular stabilizers, congenital change in the shape of acromion process, etc. are one of the major causes of SAIS. And understanding its root cause will be very helpful in the diagnosis and management. Hence, this article provides a brief overview for quick clinical assessment and management of SAIS based upon the pathomechanics of SAIS.

The drastic changes regarding the growth in demand for pharmacists in healthcare and patient needs have been significant in parallel to the redefinition of the educational and professional responsibilities of pharmacists. Irrational use of antibiotics is one of the major problems for many developing countries and  the rapid growth of antibiotic resistance is widely acknowledged. Irrational practice of antibiotics comprises prescription of incorrect dose, duration, route of administration, and regimen frequency and are influenced by certain interrelated factors and drivers. The primary complications of irrational antibiotic use are antibiotic resistance with an increase in poorer health outcomes, increased healthcare costs, more extended hospitalization, and higher mortality, particularly in the pediatric population. WHO identified India as one of the top countries with higher rates of antibiotic resistance globally with proven reports of inappropriate and irrational use of antibiotics resulting in increased incidence and the threat of antimicrobial resistance. The scope of clinical pharmacy delineates the promising use of antibiotics more rationally than ever. Clinical pharmacists are responsible for achieving goals by spreading awareness and educating about optimal drug use to govern pharmaceutical promotions at the hospital, subsequently progressing outcomes. The narrative review aimed to discuss major influencing factors and compilations associated with irrational antibiotic use, concerns in the pediatric population regarding pharmacokinetic/pharmacodynamic characteristics, and the contribution of clinical pharmacist intervention in addressing the global concern of irrational antibiotic use. Clinical pharmacist services can help to determine appropriate antibiotic dosing regimens in pediatric populations concerning physiological and anatomical changes.

Labyrinthine fistula (LF) is a pathological condition with abnormal communication between the inner ear and the middle/mastoid cavity. LF usually depends on cholesteatoma and may cause hearing loss, dizziness, and facial palsy. 

Surgical management is the treatment of choice since hearing preservation and the technique to perform are a source of debate.

Some authors retain the cholesteatoma matrix on the side of LF to avoid damage to cochlear function. The other management claims to totally remove cholesteatoma, repairing the labyrinth with bone sealing. In cases of cholesteatoma matrix removal, the fistula is commonly covered without suctioning and without drilling the bone labyrinth to reduce the risk of hearing. 

In 2008, Magliulo et al. proposed a partial labyrinthectomy as a safe technique to treat LF with hearing preservation, performing the total removal of the cholesteatoma matrix and involving bone cover. This procedure may also be used in petrous bone cholesteatoma to preserve the labyrinth's anatomic structure and functional activity. The results showed a high rate of hearing preservation in both cases, which was also proved by radiological imaging. Therefore, the strength of this technique lies in the respect of the inner ear's anatomic structure and functional activity.

Background: The prevalence of obesity and atrial fibrillation (AF), which are inextricably linked, is rapidly increasing worldwide. Recent studies suggest that effectiveness of weight loss in reducing AF risk. Therefore, it is necessary to unravel the nexus between obesity and atrial fibrillation.

Purpose: The focus of this review is to discuss the epidemiology of obesity and AF, summarize the mechanisms by which obesity triggers AF, and emphasize how weight loss improves the prognosis of AF.

Results: Epidemiological data indicates obese patients are more likely to develop AF, but there is still controversy. The underlying mechanism of obesity leading to atrial fibrillation is quite complex. Obesity-related hypertension, diabetes, and obstructive sleep apnea are associated with AF. Additionally, increased epicardial fat, systemic inflammation, and oxidative stress caused by obesity can induce atrial enlargement, inflammatory activation, local myocardial fibrosis, and electrical conduction abnormalities, all of which led to AF and promoted its persistence. Weight loss reduced the risk and reversed natural progression of AF, However, fluctuations in weight offset the benefits of weight loss. Therefore, the importance of steady weight loss urges clinicians to incorporate weight management interventions in the treatment of patients with AF.

Introduction: Infective endocarditis (IE) is a very heterogeneous condition for several reasons. The diagnosis can be notoriously difficult. A delay in diagnosis can have severe consequences. Even proper application of the Duke criteria cannot solve all cases. For this reason, positron emission tomography / computer tomography (PET/CT) with 18F-fluorodesoxyglucose (18FDG) has been proposed in the 2015 guidelines of the European Society of Cardiology. What has been the effect of these guidelines thus far?

Methods: A probe of the literature has been performed in PubMed, from 2016 on using the search terms “endocarditis AND PET”. PET with 18-fluoro-desoxyglucose (18-FDG) as marker for increased metabolism can serve such as in inflammation, infection and malignancies.

Results: One hundred items were identified, of which 41 documents could be retained. However, only 16 were original series, mostly with low numbers. The other manuscripts were editorials, comments, reviews and “image vignettes”. PET/CT increased the sensitivity of the Duke criteria in cases of prosthetic valve endocarditis (PVE), but in a much lesser degree in native valve endocarditis (NVE). Patient preparation should be standardized in order to reduce the uptake of 18FDG by the myocardium. This includes low carbohydrate – high fat diet, fasting and unfractionated heparin administration. Furthermore, image acquisition and processing (quantification, correction for attenuation, taking into account implanted metallic materials) should also be standardized. Infection and inflammation of other causes such as postoperative healing and foreign body reaction should be discerned because of their different management and outcome. Scintigraphic techniques, based on radiolabeled WBC can serve as complement for distinction between sterile inflammation and infection. Effects of antibiotics (negative imaging results before cure) and inflammation (especially healing after operation and use of biological glue materials) should be taken into account. Radiolabeled white blood cell scintigraphy could be a valuable adjunct in these cases. The detection of extra- cardiac foci (especially tumors which can serve as port of entry and septic emboli) is an additional advantage.

Conclusion: PET/CT seems a valuable tool to increase the accuracy in diagnosing IE, especially PVE. Early postoperative cases must be interpreted with caution. To confirm the value of PET/CT, the major centers should standardize their method. This allows comparison of results of larger patient groups, which could be collected in the International Collaboration of Endocarditis – Prospective Cohort Study. A standardized method for patient preparation, imaging acquisition and processing is needed. This can best be undertaken through the International Collaboration on Endocarditis– Prospective Control Study ICE-PCS. Nuclear cardiologists should also be included in “endocarditis teams.

The present study investigates a QTc interval prolongation in diagnosed cases of Diabetic Ketoacidosis with reference to electrolyte imbalances. Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are dangerous manifestations of diabetes mellitus representing two extremes in the spectrum of uncontrolled diabetic state. DKA occurs predominantly in those with type 1 diabetes. The basic defect in the pathogenesis of DKA is insulin deficiency. DKA accounts for 14 percentages of all hospital admissions among diabetics and 16 percentages of all diabetes- related fatalities in India. The study was conducted in the ICU, general medicine ward and casualty under Department of Medicine at tertiary care hospital during August 2020 to July 2022. In present study QTc Maximum mean ±SD found in electrolytes abnormal group was 441.11 ± 16.49 and in electrolytes normal group was 424.41 ± 21.30, QTc Minimum mean ±SD found in electrolytes abnormal group was 393.69 ± 8.24 and in electrolytes normal group was 383.08 ± 15.99. QTc Dispersion mean ±SD found in electrolytes abnormal group was 48.75 ± 9.22 and in electrolytes normal group was 41.63 ± 9.88. QTc Mean mean ±SD found in electrolytes abnormal group was 417.41 ± 12.35 and in electrolytes normal group was 404.65 ± 15.81. HbA1c level was found between 7 to 10 in (77 %) cases and >10 in (23 %) cases. In Group A HbA1c mean ±SD was 9.2 ± 0.41 and in Group B it was 9.6 ± 0.605. There was statistically significant correlation between HbA1c and QTc interval prolongation. It is suggested that QTc interval prolongation is an indicator of CAN (Cardiac Autonomic Neuropathy) and predictive tool for cardio-vascular mortality (worse outcomes) in patients with Diabetic Ketoacidosis.

Background: Medulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor clinical outcomes and respond poorly to current therapies. Epigenetic deregulation is very common in MYC- driven MB. The bromodomain extra-terminal (BET) proteins and histone deacetylases (HDACs) are epigenetic regulators of MYC transcription and its associated tumorigenic programs. This study aimed to investigate the therapeutic potential of inhibiting the BET proteins and HDACs together in MB.

Aim: The study explores the potential of dual-inhibition targeting BET proteins and HDACs, both of which play crucial roles in MYC transcription and tumorigenic programs.

Methods: Using clinically relevant BET inhibitors (JQ1 or OTX015) and a pan-HDAC inhibitor (panobinostat), we evaluated the effects of combined inhibition on cell growth/survival in MYC-amplified MB cell lines and xenografts and examined underlying molecular mechanism(s). Single agent and combined efficacies of these inhibitors on MB cell growth, apoptosis and cell cycle were determined using MTT, Annexin-V and propidium-iodide staining assays, respectively. Underlying mechanisms of these efficacies were investigated using RNA-seq, siRNA-transfection, RT-PCR and western blot analyses. In vivo antitumor efficacies were evaluated using subcutaneously MB-bearing xenografts.

Results: Co-treatment of JQ1 or OTX015 with panobinostat synergistically suppressed growth/survival of MYC- amplified MB cells by inducing G2 cell cycle arrest and apoptosis. Mechanistic investigation using RNA-seq revealed that co-treatment of JQ1 with panobinostat synergistically modulated global gene expression including MYC/HDAC targets. SYK and MSI1 oncogenes were among the top 50 genes synergistically downregulated by JQ1 and panobi- nostat. RT-PCR and western blot analyses confirmed that JQ1 and panobinostat synergistically inhibited the mRNA and protein expression of MSI1/SYK along with MYC expression. Reduced SYK/MSI expression after BET (specifically, BRD4) gene-knockdown further confirmed the epigenetic regulation of SYK and MSI1 genes. In addition, the combi- nation of OTX015 and panobinostat significantly inhibited tumor growth in MYC-amplified MB xenografted mice by downregulating expression of MYC, compared to single-agent therapy.

Conclusions: Together, our findings demonstrated that dual-inhibition of BET and HDAC proteins of the epigenetic pathway can be a novel therapeutic approach against MYC-driven MB. The findings demonstrate the synergistic effects of this combination therapy in suppressing MB cell growth and survival, providing valuable insights into potential treatment strategies for MYC-driven MB and highlighting the importance of epigenetic regulation in this context. On the other hand, this is a significant finding that could lead to the development of new treatments for this devastating disease.

Dentistry has traditionally transitioned from the straightforward extraction of the caries-affected tooth to the treatment and restoration of the lesion in the evolution of caries therapy. A further development in dental care is the detection of early caries lesions and treatment using non-surgical techniques like remineralization. The phrases early childhood caries and rampant caries are occasionally used interchangeably. More than 25 secreted and membrane-bound enzymes collectively referred to as matrix metalloproteinases are a class of enzymes that break down pericellular substrates. The amount of free radicals scavenged by a test solution is measured as the total antioxidant capacity, which is then used to assess the antioxidant strength of biological samples. This is very important because oxidative stress can influence the beginning and development of various nflammatory and infectious disorders, including dental caries. The purpose of this review is to talk about how total antioxidant capacity and matrix metalloproteases relate to early childhood caries.