Decoding the Therapeutic Potential of Cannabis and Cannabinoids in Neurological Disorders.

For millennia, Cannabis sativa has served diverse roles, from medicinal applications to recreational use. Despite its extensive historical use, only a fraction of its components have been explored until recent times. The therapeutic potential of Cannabis and its constituents has garnered attention, with suggestions for treating various conditions such as Parkinson's disease, epilepsy, Alzheimer's disease, and other Neurological disorders. Recent research, particularly on animal experimental models, has unveiled the neuroprotective properties of cannabis. This neuroprotective effect is orchestrated through numerous G protein-coupled receptors (GPCRs) and the two cannabinoid receptors, CB1 and CB2. While the capacity of cannabinoids to safeguard neurons is evident, a significant challenge lies in determining the optimal cannabinoid receptor agonist and its application in clinical trials. The intricate interplay of cannabinoids with the endocannabinoid system, involving CB1 and CB2 receptors, underscores the need for precise understanding and targeted approaches. Unravelling the molecular intricacies of this interaction is vital to harness the therapeutic potential of cannabinoids effectively. As the exploration of cannabis components accelerates, there is a growing awareness of the need for nuanced strategies in utilizing cannabinoid receptor agonists in clinical settings. The evolving landscape of cannabis research presents exciting possibilities for developing targeted interventions that capitalize on the neuroprotective benefits of cannabinoids while navigating the complexities of receptor specificity and clinical applicability.

Infectious etiology of intussusception in Indian children less than 2 years old: a matched case-control analysis.

BACKGROUND: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens. METHODS: In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception. RESULTS: The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06-2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05-2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% - 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% - 24.1%) had the highest population attributable fraction for intussusception. CONCLUSION: Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.

Unleashing the power of silk-based proteins as biomaterials for cutting-edge drug delivery: a comprehensive review.

Silk proteins, viz., sericin, fibroin and their modified forms etc., have been thoroughly researched as natural biopolymers for the development of varied nanomaterials exhibiting diverse biomedical applications. The silk proteins are extracted from the cocoons by degumming and treatment with soaps, followed by dissolution and dialysis against water. These proteins exhibit distinct mechanical and physicochemical characteristics including biocompatibility, controlled biodegradability, self-assembling traits, chemical modifiability, and adaptability, thus making it an ideal drug delivery vehicle. In this regard, silk protein-derived drug delivery systems have been reported as efficient carrier to encapsulate and stabilize the wide variety of pharmacological molecules, enzymes, proteins, vaccines, and even DNA, allowing them to remain active for a longer period of time. Further, different delivery carriers researched employing these proteins for multitude of applications include hydrogels, sponges, fibres, scaffolds and particulate delivery systems. Additionally, the chemical modification of silk proteins has further opened avenues for development of other modified silk proteins with improved physicochemical traits and hence exhibiting enormous potential in development of varied bioenhanced carrier systems. The current article thus provides the holistic information of characteristics, types of silk protein-based delivery carriers, and their fabrication techniques, while emphasizing the applications of different silk proteins in biomedicine and drug delivery.

Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation.

Parkinson's disease is a progressive neurodegenerative disease that affects the motor and non-motor circuits of the brain. Currently, there are no promising therapeutic measures for Parkinson's disease, and most strategies designed to alleviate the Parkinson's disease are palliative. The dearth of therapeutic interventions in Parkinson's disease has driven attention in the search for targets that may augment dopamine secretion, promote differentiation towards dopaminergic neuronal lineage, or aid in neuroprotection from neuronal stress and inflammation, and prevent Parkinson's disease associated motor impairment and behavioural chaos. The study first reports that Rev-erbα plays an important role in regulating the differentiation of undifferentiated neuronal cells towards dopaminergic neurons through abating Sox2 expression in human SH-SY5Y cells. Rev-erbα directly binds to the human Sox2 promoter region and represses their expression to promote differentiation towards dopaminergic neurons. We have reported a novel mechanism of Rev-erbα which effectively abrogates 1-methyl-4-phenylpyridinium induced cytotoxicity, inflammation, and oxidative stress, exerted a beneficial effect on transmembrane potential, and suppressed apoptosis in the neuronal in vitro model of Parkinson's disease. Rev-erbα ligand SR9011 was observed to ease the disease severity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mouse model of Parkinson's disease. Rev-erbα alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erbα ligand also helps in replenishing the dopaminergic neurons and abrogating the neurotoxin mediated toxicity in an in vitro and in vivo Parkinson's disease model. We conclude that Rev-erbα emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.

Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression.

ABSTRACT: The regulation of red blood cell (RBC) homeostasis by erythropoietin (EPO) is critical for O2 transport and maintaining the adequate number of RBCs in vertebrates. Therefore, dysregulation in EPO synthesis results in disease conditions such as polycythemia in the case of excessive EPO production and anemia, which occurs when EPO is inadequately produced. EPO plays a crucial role in treating anemic patients; however, its overproduction can increase blood viscosity, potentially leading to fatal heart failure. Consequently, the identification of druggable transcription factors and their associated ligands capable of regulating EPO offers a promising therapeutic approach to address EPO-related disorders. This study unveils a novel regulatory mechanism involving 2 pivotal nuclear receptors (NRs), Rev-ERBA (Rev-erbα, is a truncation of reverse c-erbAa) and RAR-related orphan receptor A (RORα), in the control of EPO gene expression. Rev-erbα acts as a cell-intrinsic negative regulator, playing a vital role in maintaining erythropoiesis at the correct level. It accomplishes this by directly binding to newly identified response elements within the human and mouse EPO gene promoter, thereby repressing EPO production. These findings are further supported by the discovery that a Rev-erbα agonist (SR9011) effectively suppresses hypoxia-induced EPO expression in mice. In contrast, RORα functions as a positive regulator of EPO gene expression, also binding to the same response elements in the promoter to induce EPO production. Finally, the results of this study revealed that the 2 NRs, Rev-erbα and RORα, influence EPO synthesis in a negative and positive manner, respectively, suggesting that the modulating activity of these 2 NRs could provide a method to target disorders linked with EPO dysregulation.

Impact of Bioactive Compounds in the Management of Various Inflammatory Diseases.

Inflammation is an individual's physiological response to a sequence of physical, chemical, or infectious stressors acting mainly to provide localized protection. Although inflammation is a protective and thus beneficial process, its excess or prolonged action can be harmful to the body. An increasing number of the population worldwide are changing their lifestyles, which leads to a rise in inflammatory diseases, such as atherosclerosis, angina pectoris, myocardial infarction, ulcerative colitis, cancer, and many more. Their treatment is based majorly on the pharmacological approach. However, natural products or bioactive compounds are of great significance in inflammation therapy because they show minimum side effects and maximum bioavailability. Therefore, it is critical to investigate bioactive substances that can modify target functions associated with oxidative stress defense and might be used to achieve various health benefits. This review accentuates the essence of bioactive chemicals used in the treatment of inflammation and other inflammatory illnesses. These bioactive compounds can be of any origin, such as plants, animals, bacteria, fungi, marine invertebrates, etc. Bioactive compounds derived from plant sources, such as glycyrrhizin, lignans, lycopene, resveratrol, indoles, and phenolic and polyphenolic compounds, work mainly by reducing oxidative stress and thereby preventing various inflammatory disorders. A large diversity of these anti-inflammatory bioactive compounds has also been discovered in marine environments, giving rise to an increase in the interest of various scientists in marine invertebrates and microbes. The vast diversity of microbes found in the marine environment represents an enormous supply to extract novel compounds, such as from bacteria, cyanobacteria, fungi, algae, microalgae, tiny invertebrates, etc. In the present review, an attempt has been made to summarize such novel bioactive compounds that help prevent inflammatory responses via different mechanisms of action.

Unveiling the phyto-restorative potential of ethereal distillates for atopic dermatitis: an advanced therapeutic approach.

Atopic dermatitis is acknowledged as a vital inflammatory disorder associated with the integumentary system of the body and is characterized by the formation of thick reddish-grey scars and erythema formation on skin, prevalent amidst the populace. Numerous synthetic drugs are available for treatment like antihistamines, immunosuppressants, glucocorticoids etc., but contrarily, essential oil therapy is exclusively lime lighted to favour the purpose. The utilization of available engineered drugs, possess the marked adverse effects owing to prolonged duration of therapy and therefore, essential oils are explored well and proved to exhibit the anti-eczematic, anti-inflammatory and antipruritic properties. Ethereal distillates own the assorted and selective therapeutic properties attributable to presence of bioactive compounds liable to treat this torturous and integumentary disorder, likely lavender oil, patchouli oil, frankincense oil etc., have been found to exert their pharmacological actions by impeding the liberation and action of inflammatory mediators and immunological hyperactivities that are engaged in exacerbating this idiopathic illness. The current attempt provided the update with the aim to bring forth the naturally originated treatment that is pertinent to provide the invulnerable therapy by circumventing the noxious symptoms i.e. erythema formation and inflamed lesions.

Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's.

Elevated ER stress has been linked to the pathogenesis of several disease conditions including neurodegeneration. In this study, we have holistically determined the differential expression of all the nuclear receptors (NRs) in the presence of classical ER stress inducers. Activation of Nr1h4 and Thrb by their cognate ligands (GW4064 and T3) ameliorates the tunicamycin (TM)-induced expression of ER stress genes. A combination of both ligands is effective in mitigating cell death induced by TM. Further exploration of their protective effects in the Parkinson's disease (PD) model shows that they reduce MPP+-induced dissipation of mitochondrial membrane potential and ROS generation in an in vitro PD model in neuronal cells. Furthermore, the generation of an experimental murine PD model reveals that simultaneous treatment of GW4064 and T3 protects mice from ER stress, dopaminergic cell death, and functional deficits in the MPTP mouse model of PD. Thus, activation of Nr1h4 and Thrb by their respective ligands plays an indispensable role in ER stress amelioration and mounts protective effects in the MPTP mouse model of PD.

Marine-derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating form of dementia that primarily affects cholinergic neurons in the brain, significantly reducing an individual's capacity for learning and creative skills and ultimately resulting in an inability to carry out even basic daily tasks. As the elderly population is exponentially increasing, the disease has become a significant concern for society. Therefore, neuroprotective substances have garnered considerable interest in addressing this universal issue. Studies have shown that oxidative damage to neurons contributes to the pathophysiological processes underlying AD progression. In AD, tau phosphorylation and glutamate excitotoxicity may play essential roles, but no permanent cure for AD is available. The existing therapies only manage the early symptoms of AD and often come with numerous side effects and toxicities. To address these challenges, researchers have turned to nature and explored various sources such as plants, animals, and marine organisms. Many historic holy books from different cultures emphasize that adding marine compounds to the regular diet enhances brain function and mitigates its decline. Consequently, researchers have devoted significant time to identifying potentially active neuroprotective substances from marine sources. Marine-derived compounds are gaining recognition due to their abundant supply of diverse chemical compounds with biological and pharmacological potential and unique mechanisms of action. Several studies have reported that plants exhibit multitarget potential in treating AD. In light of this, the current study focuses on marine-derived components with excellent potential for treating this neurodegenerative disease.

Exploring the Intersection of Geophysics and Diagnostic Imaging in the Health Sciences.

To develop diagnostic imaging approaches, this paper emphasizes the transformational potential of merging geophysics with health sciences. Diagnostic imaging technology improvements have transformed the health sciences by enabling earlier and more precise disease identification, individualized therapy, and improved patient care. This review article examines the connection between geophysics and diagnostic imaging in the field of health sciences. Geophysics, which is typically used to explore Earth's subsurface, has provided new uses of its methodology in the medical field, providing innovative solutions to pressing medical problems. The article examines the different geophysical techniques like electrical imaging, seismic imaging, and geophysics and their corresponding imaging techniques used in health sciences like tomography, magnetic resonance imaging, ultrasound imaging, etc. The examination includes the description, similarities, differences, and challenges associated with these techniques and how modified geophysical techniques can be used in imaging methods in health sciences. Examining the progression of each method from geophysics to medical imaging and its contributions to illness diagnosis, treatment planning, and monitoring are highlighted. Also, the utilization of geophysical data analysis techniques like signal processing and inversion techniques in image processing in health sciences has been briefly explained, along with different mathematical and computational tools in geophysics and how they can be implemented for image processing in health sciences. The key findings include the development of machine learning and artificial intelligence in geophysics-driven medical imaging, demonstrating the revolutionary effects of data-driven methods on precision, speed, and predictive modeling.

Bioactive Compound-Loaded Nanocarriers for Hair Growth Promotion: Current Status and Future Perspectives.

Hair loss (alopecia) has a multitude of causes, and the problem is still poorly defined. For curing alopecia, therapies are available in both natural and synthetic forms; however, natural remedies are gaining popularity due to the multiple effects of complex phytoconstituents on the scalp with fewer side effects. Evidence-based hair growth promotion by some plants has been reported for both traditional and advanced treatment approaches. Nanoarchitectonics may have the ability to evolve in the field of hair- and scalp-altering products and treatments, giving new qualities to hair that can be an effective protective layer or a technique to recover lost hair. This review will provide insights into several plant and herbal formulations that have been reported for the prevention of hair loss and stimulation of new hair growth. This review also focuses on the molecular mechanisms of hair growth/loss, several isolated phytoconstituents with hair growth-promoting properties, patents, in vivo evaluation of hair growth-promoting activity, and recent nanoarchitectonic technologies that have been explored for hair growth.

Understanding the promising role of antibody drug conjugates in breast and ovarian cancer.

A nascent category of anticancer therapeutic drugs called antibody-drug conjugates (ADCs) relate selectivity of aimed therapy using chemotherapeutic medicines with high cytotoxic power. Progressive linker technology led to the advancement of more efficacious and safer treatments. It offers neoteric as well as encouraging therapeutic strategies for treating cancer. ADCs selectively administer a medication by targeting antigens which are abundantly articulated on the membrane surface of tumor cells. Tumor-specific antigens are differently expressed in breast and ovarian cancers and can be utilized to direct ADCs. Compared to conventional chemotherapeutic drugs, this approach enables optimal tumor targeting while minimizing systemic damage. A cleavable linker improves the ADCs because it allows the toxic payload to be distributed to nearby cells that do not express the target protein, operating on assorted tumors with dissimilar cell aggregation. Presently fifteen ADCs are being studied in breast and ovarian carcinoma preclinically, and assortment of few have already undergone promising early-phase clinical trial testing. Furthermore, Phase I and II studies are investigating a wide variety of ADCs, and preliminary findings are encouraging. An expanding sum of ADCs will probably become feasible therapeutic choices as solo agents or in conjunction with chemotherapeutic agents. This review accentuates the most recent preclinical findings, pharmacodynamics, and upcoming applications of ADCs in breast and ovarian carcinoma.

Evolving Advances in the Cosmetic Use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects.

Ongoing development in cosmetics is increasingly making use of probiotics, which are defined as "live microorganisms with health-enhancing properties mediated through ingestion or topical application to the host". The observation that several bacterial strains augment normal processes of healthy tissue maintenance, particularly for the skin, has opened up new avenues for the use of bacterial strains in cosmetics. A principal feature of such "cosmeceuticals" is an application of increasing insight into the biochemical nature of the skin's normal microbial flora, also called its microbiome. The opportunity of manipulating the skin microbiome to address various skin disorders has revealed novel routes for treatment. The skin microbiome manipulation approaches to address various skin disorders include skin microbiome transplantation, skin bacteriotherapy, and prebiotic stimulation. Research in this field has revealed that medical outcome-targeted manipulation of skin microbiome bacterial strain makeup may significantly increase skin health and appearance. Commercial availability of probiotic skincare products is rapidly expanding worldwide due to satisfactory laboratory results and public perception of probiotics as being intrinsically more wholesome than other bioactive substances, such as synthetics. Major outcomes of probiotic use include a significant reduction in skin wrinkling, acne and other conditions adversely affecting skin appearance and healthy function. Moreover, probiotics may additionally promote normal skin hydration, resulting in a vibrant and lustrous appearance. Nevertheless, significant technical challenges remain for the full optimization of probiotics in cosmetic products. This article summarizes the evolving nature of this field and explores current probiotic research initiatives, along with regulatory aspects and significant challenges in the manufacturing of cosmetics in the context of market expansion for these products.

Effect of Normal Saline versus PlasmaLyte on Coagulation and Metabolic Status in Patients Undergoing Neurosurgical Procedures.

Background The choice of intraoperative fluid in neurosurgical patients is important as we need to maintain adequate cerebral perfusion and oxygenation and also avoid cerebral edema. Normal saline (NS) is commonly used in neurosurgeries, but it leads to hyperchloremic metabolic acidosis, which may result in coagulopathy. Balanced crystalloid with physiochemical composition akin to that of plasma has favorable effects on metabolic profile and may avoid the problems associated with NS. Against this background, the present study aimed to compare the effects of NS versus PlasmaLyte (PL) on coagulation profile in patients undergoing neurosurgical procedures. Methods This prospective, randomized, double-blinded study was conducted in 100 adult patients scheduled to undergo various neurosurgical procedures. Patients were randomly allocated in two groups of 50 each to receive either NS or PL intraoperatively and postoperatively till 4 hours after the surgery. Hemoglobin, hematocrit, coagulation profile (PT, PTT, and INR), serum chloride, pH, blood urea, and serum creatinine were measured prior to induction (baseline) and 4 hours after completion of surgery. Results Demographic characteristics were statistically similar between the two groups. Coagulation profile parameters were comparable between the two groups at baseline as well as 4 hours after surgery. pH was significantly lower in the NS group as compared to the PL group at 4 hours after surgery. Postoperatively blood urea, serum creatinine, and serum chloride levels were significantly raised in the NS group as compared to the PL group. Hemoglobin and hematocrit values were similar between the two groups. Conclusion Coagulation profile parameters were normal and statistically similar with intraoperative infusion of NS versus PL in patients undergoing neurosurgical procedures. However, use of PL was associated with a better acid-base and renal profile in these patients.

Alkaloids as Potential Anti-HIV Agents.

BACKGROUND: Alkaloids are nitrogen-containing compounds that are naturally occurring and have a variety of biological activities, including antimicrobial properties. In this study, the authors used a molecular docking approach to evaluate the anti-HIV potential of 64 alkaloids. METHODS: The authors used the Molegro Virtual Docker software to dock the alkaloids into the active sites of three HIV enzymes: protease, integrase, and non-nucleoside reverse transcriptase (NNRT). The docking scores were used to assess the potential of the alkaloids to inhibit the enzymes. RESULTS: The results showed the alkaloids to have good potential to inhibit the enzymes. Tubocurarine and reserpine were found to be the most potent alkaloids, with docking scores of -123.776 and - 114.956, respectively. CONCLUSION: The authors concluded that tubocurarine and reserpine could be further promoted as potential lead molecules for the development of new anti-HIV drugs.

Role of Routine Blood Parameters in Predicting Mortality Among Surgical Patients With Sepsis.

BACKGROUND: Outcome prediction for surgical patients with sepsis may be conducive to early aggressive interventions. In several studies, changes in the level of numerous biomarkers like red cell distribution width (RDW), platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) have been demonstrated to be associated with mortality in critically ill patients. We aimed at investigating the prognostic significance of dynamic changes in RDW, PC, MPV, and PDW in surgical patients with sepsis. METHODS: We prospectively enrolled 110 surgical patients of sepsis in our study admitted to the surgical ward and ICU. We measured RDW, PC, MPV, and PDW on days 1, day 4, and day 8. Receiver operating characteristics (ROC) were generated for prognostic validation of these parameters and mortality in surgical patients with sepsis.  Results: We found that higher RDW and PDW on day 1 among non-survivors as compared to survivors on day 1 were significantly associated with mortality. ROC curves showed that RDW and PDW on day 1 could be used to predict mortality in surgical patients with sepsis and it was dynamic changes in PC on day 4 and day 8 along with a change in MPV on day 8, which was significantly associated with mortality. CONCLUSION: The major findings of our study were baseline value of RDW and PDW on day 1 and continuous decrease in PC and increase in MPV over one week were significantly associated with mortality. So, it is better to monitor dynamic changes in PC and MPV in combination with baseline RDW and PDW. So, these parameters can be promising markers to assess prognosis in surgical patients with sepsis.

White Coat Effect: Is It Because of the Hospital Setting, or Is It Physician-Induced?

INTRODUCTION: White coat hypertension (WCH) patients are those individuals who have high blood pressure (BP) in the medical environment but are normal during their daily activities. White coat hypertensive patients with normal daytime ambulatory blood pressure monitoring (ABPM) rapidly progress to sustained hypertension. WCH is mainly treated with non-pharmacological methods. Alpha-1 agonists and beta blockers are logical treatment choices for patients with fixed hypertension with the White Coat Effect (WCE). Masked hypertension patients are those individuals who have normal values at the doctor's office but elevated BP at home or during 24-hour ABPM (24-hour or daytime). ABPM is a more practical and reliable method for detecting patients with WCH. MATERIAL AND METHODS: This observational study was conducted at Dayanand Medical College & Hospital, Ludhiana, over the course of one year (December 2015 to November 2016). The primary objective of the study was to determine whether there was a difference in blood pressure readings between the home setting and the hospital setting. The secondary objective was to determine whether the difference, if present, between the hospital and home readings was due to the hospital setting, physician presence, or a combination of both. Patients with stage 1 hypertension were included in the study, irrespective of antihypertensive treatment. Patients with ischemic heart disease, chronic liver failure, and chronic kidney disease who could not follow protocol instructions were excluded. RESULTS: In our study, the mean age of patients was 53.91±12.86 years. The patient's mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings at the hospital were higher than their home readings (p-0.012; p-0.001, respectively). Mean hospital SBP and DBP readings recorded by the physician were higher than readings recorded by patients alone at home (p-0.002; p-0.014, respectively) and alone at the hospital (p-0.004; p-0.001, respectively). BP readings taken by the physician with a manual sphygmomanometer were significantly lower than those taken with a digital sphygmomanometer by patients and physicians in all settings (p<0.05). The mean rise in BP was significant in both the physician's presence and the hospital environment (p<0.05 for both), and this rise was more significantly associated with the hospital effect than the physician effect (p<0.05). CONCLUSION: Misdiagnosis of hypertension results in inappropriate prescription and overuse of antihypertensive medications for individuals who are not persistently hypertensive. So it is very important to rule out WCH in both the hospital setting and the physician's presence, more precisely by ABPM. WCH can be diagnosed with regular BP monitoring by a digital sphygmomanometer at home.

Risk Factors and Outcome Analysis of Gram-Positive Bacteremia in Critically Ill Patients.

Introduction Bloodstream infection (BSI) is a common problem for patients in the intensive care unit (ICU). Nearly 60% of primary bloodstream infections are caused by Gram-positive cocci. Gram-positive bacteria gain access to the bloodstream through invasive procedures and various patient care equipment like catheters, intravenous lines, and mechanical ventilators. S. aureus is considered to be the major cause of septicemia. Knowledge of healthcare-associated infections and the antimicrobial susceptibility patterns of the isolates are crucial in guiding empirical treatment. Methods This prospective observational study was conducted in Medical ICU, Dayanand Medical College & Hospital, Ludhiana over a period of one year (December 2015 to November 2016). Patients whose blood cultures tested positive for Gram-positive bacteria were included in the study. This study was carried out to assess the implications and risk factors for nosocomial BSI and several factors, including the age of the patient, the severity of illness, the presence of catheters, and the microorganisms causing the BSI to independently predict mortality. Chief complaints and risk factors were evaluated. APACHE-II scores were calculated for all patients and outcomes were analyzed. Results In our study, the mean age of patients was 50.93±14.09 years. Central line insertion was found as the most common risk factor (58.7%). A statistically significant correlation was obtained between APACHE-II scores and the presence of risk factors i.e. central line insertion (p-value=0.010) and diabetes mellitus (p-value=0.003). The most common Gram-positive pathogen isolated by blood culture was methicillin-sensitive S. aureus (44.2%). For management, the majority of the patients were prescribed teicoplanin (58.7%). The 28-day overall mortality rate in our study was 52.9%. Conclusion We conclude that independent risk factors like diabetes mellitus, central line insertion, and acute pancreatitis in adult patients with Gram-positive bacteremia were associated with higher mortality. We have also concluded that the administration of early appropriate antibiotics improves patient outcomes.

Financing for Sustainable Development Goals (SDGs) in the Era of COVID-19 and Beyond.

The economic and social impact of covid-19 pandemic both on developing and developed countries has been significant. In addition to the impact of the pandemic, the current Ukraine war has also led to severe supply chain disruptions leading to a sharp increase in food and commodity prices globally. Due to a combination of external shocks and the impact of the pandemic global economic growth is expected to slow down from 6.1% in 2021 to 3.2% in 2022 and further to 2.7% in 2023 (IMF in: World economic outlook, International Monetary Fund, 2022). The above factors have led to a sharp increase in government expenditure constraining both developed and developing countries' fiscal capacity. This has further implications for the achievement of SDGs especially for low-income countries. The challenge for developing countries in the current scenario is to mobilise adequate resources both from domestic and international sources, not just for the achievement of SDGs as such, but also to sustain the livelihoods, health, and welfare of people. This special issue aims to examine some of these issues in the context of developing countries.

L'impact économique et social de la pandémie de COVID-19, tant sur les pays en développement que sur les pays développés, a été important. Outre l'impact de la pandémie, la guerre actuelle en Ukraine a également entraîné de graves perturbations de la chaîne d'approvisionnement, entraînant une forte augmentation des prix des denrées alimentaires et des matières premières dans le monde. En raison d'une combinaison entre chocs externes et impact de la pandémie, la croissance économique mondiale devrait ralentir de 6,1 % en 2021 à 3,2 % en 2022, puis à 2,7 % en 2023 (FMI 2022). Les facteurs ci-dessus ont conduit à une forte augmentation des dépenses publiques, limitant la capacité budgétaire des pays développés et en développement. Cela a d'autres implications pour la réalisation des ODD, en particulier pour les pays à faible revenu. Le défi pour les pays en développement dans le scénario actuel est de mobiliser des ressources adéquates provenant de sources nationales et internationales, non seulement pour la réalisation des ODD en tant que tels, mais aussi pour maintenir les moyens de subsistance, la santé et le bien-être des personnes. Ce numéro spécial vise à aborder certaines de ces questions dans le contexte des pays en développement.

Association of PD-L1 and p16 expression with clinicopathological parameters in oral cavity and oropharyngeal squamous cell carcinoma.

BACKGROUND: High expression of PD-L1 in tumour cells is associated with a higher response rate to immune checkpoint inhibitors, which target T regulatory pathways. p16 is a surrogate marker for human papilloma virus associated cancers. The present study was conducted to evaluate PD-L1 and p16 expression in head and neck squamous cell carcinomas and its correlation with clinicopathological parameters. MATERIALS AND METHODS: Histologically confirmed cases of head and neck squamous cell carcinomas were evaluated for PD-L1 and p16 expression along with its correlation with grade and site of the tumour. RESULTS: Out of 40 cases, 21 (52.5 %) showed positive immunoreactivity for PD-L1 while 13 (32.5 %) were positive for p16. A significant association was observed between PD-L1 and p16 expression in the oropharynx (p value= 0.035). No significant association could be established between clinicopathological parameters and PD-L1/ p16 expression or between PD-L1 and p16 in the oral cavity. CONCLUSION: PD-L1 expression shows a positive association with p16 in oropharyngeal squamous cell carcinomas. Immune checkpoint inhibitors against PD-L1 can be used in carcinomas with positive expression for PD-L1.