Evaluation of non-invasive diagnostic tools for diarrhea: a systematic review of point-of-care tests and biomarkers.

Background: Diarrhea is a prevalent condition affecting millions worldwide. However, current standard diagnostic methods have many drawbacks. This review examines various non-invasive point-of-care (POC) tests and biomarkers aiding rapid diagnosis of diarrhea from different causes. Methods: PubMed, PubMed Central, ScienceDirect, Cochrane Library, and Google Scholar were searched from 2013 to present for relevant literature. Two reviewers independently assessed included studies' quality using the Critical Appraisal Skills Programme (CASP) checklist. Results: The search yielded 1453 studies, of which 39 were included after screening and applying eligibility criteria. Polymerase chain reaction (PCR) was the POC test in 25 studies, providing consistent sensitivity and specificity. For biomarkers, C-reactive protein (CRP), fecal calprotectin, and procalcitonin offered high sensitivity and specificity for conditions like acute pediatric diarrhea, microscopic colitis, and inflammatory diarrhea, respectively. Conclusion: PCR proved the ideal POC test for rapid diarrhea diagnosis, while the procalcitonin biomarker helps differentiate inflammatory from non-inflammatory diarrhea. Other reviewed tools also demonstrated promising diagnostic performance, though improvements in sensitivity, specificity, and usability are still needed.

Risks and Warning Signs for Medical Student Suicide Mortality: A Systematic Review.

INTRODUCTION: Medical students have been known to face numerous mental health issues at disproportionately high rates. Of pertinence, medical students have been shown to have high rates of suicidal thoughts and behavior. However, little is known about the risks and warning signs for death by suicide in this group. We therefore conducted a systematic review regarding the factors associated with medical student suicide mortality. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted searches in six different databases. Studies with stratified data on at least one suicide death by a medical student were eligible for inclusion. RESULTS: Searches produced a total of 1744 articles, and of those, 13 articles were eligible for inclusion. There was a pooled total of 362 suicide deaths of medical students across five different countries. 67.6% of deaths occurred among male students, primarily in their early twenties. Students in their later years of medical school were shown to be more likely to die by suicide, as were those with a history of psychiatric issues such as depression. Motivations for suicide were academic stress/failure, harassment/bullying, and relationship issues. Warning signs for suicide among medical students were recent changes in mood/behavior and leaving a suicide note. DISCUSSION: Numerous risks and warning signs of suicide have been described in our review. Medical schools may have an important role in lowering suicide deaths by medical students; impactful change can occur through better support, changes in curriculum, and appropriate data collection.

Numerous modifiable risk factors have been linked to suicide in medical studentsWarning signs include recent changes in mood/behavior, and leaving a suicide noteMedical schools need proactive, multi-level approaches to reduce medical student suicide.

The Penn Medicine COVID-19 Therapeutics Committee-Reflections on a Model for Rapid Evidence Review and Dynamic Practice Recommendations During a Public Health Emergency.

The Penn Medicine COVID-19 Therapeutics Committee-an interspecialty, clinician-pharmacist, and specialist-front line primary care collaboration-has served as a forum for rapid evidence review and the production of dynamic practice recommendations during the 3-year coronavirus disease 2019 public health emergency. We describe the process by which the committee went about its work and how it navigated specific challenging scenarios. Our target audiences are clinicians, hospital leaders, public health officials, and researchers invested in preparedness for inevitable future threats. Our objectives are to discuss the logistics and challenges of forming an effective committee, undertaking a rapid evidence review process, aligning evidence-based guidelines with operational realities, and iteratively revising recommendations in response to changing pandemic data. We specifically discuss the arc of evidence for corticosteroids; the noble beginnings and dangerous misinformation end of hydroxychloroquine and ivermectin; monoclonal antibodies and emerging viral variants; and patient screening and safety processes for tocilizumab, baricitinib, and nirmatrelvir-ritonavir.

Trends in Tuberculosis Mortality Across India: Improvements Despite the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had significant health implications across the globe. India is a country that has faced a double burden of COVID-19 and tuberculosis (TB) since 2020. There is a need to understand the impacts of COVID-19 on tuberculosis control programs in India. Therefore, our study aimed to determine the changes in TB mortality across India between 2019 and 2021. METHODS: In our study, we described trends in TB and COVID-19 cases reported across India. Next, we compared death totals for TB between 2019, 2020, and 2021 in India at the national and state level. We considered total TB deaths, as well as deaths by TB for tribal populations, and for those living with human immunodeficiency virus (HIV). Percent changes were calculated. RESULTS: In 2020, compared to 2019, there was a 15.4% decrease in TB death totals, with 28 out of India's 36 states showing a decrease during this time period. While total deaths increased in 2021 compared to 2020, decreases did occur in 2021 compared to 2019. Deaths by TB for individuals living with HIV decreased by 16.0% across India. At a national level, there was a notable rise in TB deaths among tribal populations, though this was not universal across states. CONCLUSION: While the majority of the world has seen an increase in new TB cases and TB deaths annually since the start of the COVID-19 pandemic, there have instead been decreases in India during this time period. More research is required to understand the factors that have led to this decrease in TB deaths. Furthermore, additional allocation of resources is required to better support vulnerable populations in states where TB death totals have increased, especially among tribal populations.

A Rare Presentation of Adult-Onset Bartter Syndrome: A Case Report.

Bartter syndrome is a rare, salt-wasting tubulopathy with impaired ion reabsorption in the ascending limb of the loop of Henle, which results in hypokalemia, hypochloremia, and hypercalciuria. It usually presents in neonates, with vomiting, dehydration, and failure to thrive. It results from mutations in several genes, including KCNJ1, CLCNKB, CLCNKA, BSND, and ROMK, which encode ion transporters. We report a rare presentation of adult-onset Bartter syndrome. In this case, a 27-year-old man presented to the hospital with upper and lower limb weakness. Bartter syndrome was suspected based on serum electrolytes assessment and arterial blood gas analysis. The patient was initiated on potassium chloride (KCL) infusion and potassium chloride syrup to correct hypokalemia.

Impact of a Transition of Care Pharmacist in a Community Hospital Discharge Model.

INTRODUCTION: Pharmacists can provide a variety of discharge services that aid in transitions of care. The purpose of this study is to evaluate the impact of a pilot program implementing a unit-based clinical pharmacist at a community teaching hospital. METHODS: This prospective study evaluated pharmacist-led discharge services on an adult medicine unit over a 5-week period. The control cohort received usual care, and the intervention cohort received additional pharmacy services (e.g., counseling, medication reconciliation, ensuring medication access, and overcoming discharge barriers). The primary outcome was 30-day all-cause hospital readmissions. Secondary outcomes included emergency department (ED) utilization, Hospital Consumer Assessment of Healthcare Providers and Systems scores, and patient satisfaction survey scores. RESULTS: Overall, 197 patients were included in the control group and 210 in the intervention group. Characteristics including previous hospital utilization, comorbidity count, and medication count at discharge were similar between groups. A reduction in 30-day all-cause hospital readmissions was observed in the cohort receiving pharmacist intervention, 13.3% versus 20.8% (p = 0.044). This study also demonstrated a significant decrease in ED utilization rates and improved patient satisfaction. CONCLUSIONS: This study adds to the growing body of literature supporting transition of care pharmacists in the hospital discharge model to improve patient care.

Clinical Trial Readiness for Spinal Muscular Atrophy: Experience of an International Educational-Training Initiative.

Several successful clinical trials have been conducted in spinal muscular atrophy (SMA) over recent years which have led to the approval of splicing modifiers and gene transfer therapies. With an increasing number of other agents progressing through pre-clinical and clinical development, increasing worldwide clinical trial readiness is becoming essential.SMA Europe initiated a clinical trial readiness project, which included the development of a pilot face-to-face educational-training initiative for clinical specialists and physiotherapists involved in SMA, with an emphasis on the patient perspective. Participants were selected through two surveys and, ahead of the meeting, a mock protocol with specific questions was provided. The initiative involved a series of presentations, role-play and interactive exercises. We describe here our experience and evaluation of this educational-training initiative, emphasising scientific aspects, psychosocial implications and level of satisfaction.From a participant, patient and industry perspective, such training was considered successful and met the objective, which was to improve clinical trial readiness in emerging sites. Resource planning, ethical considerations and communication with patients were identified as three important topics for future training. This initiative highlights the need to develop a training programme to achieve clinical trial readiness across Europe and showcases a collaborative effort with different stakeholders, clinicians, patient advocacy groups and sponsors to address an important issue.

Gold(I)-Catalyzed Regioselective Cyclization to Access Cyclopropane-Fused Tetrahydrobenzochromenes.

Gold(I)-catalyzed efficient synthetic transformation was achieved to access the tetrahydrobenzo[h]cyclopropa[c]chromenes from allyl-substituted 1,6-diynes. Cyclopropane-fused tetrahydrobenzochromenes were obtained regioselectively in ≤92% yields. In this atom-economic organic transformation, three new C-C bonds were formed sequentially in one pot.

A Case of Osmotic Demyelination Syndrome in a Chronic Alcoholic With Moderate Hyponatremia.

Osmotic demyelination syndrome (ODS) is a clinical syndrome seen following aggressive correction of severe hyponatremia. Chronic alcohol use, malnutrition, and electrolyte derangement are additional risk factors promoting the demyelination in ODS. A 49-year-old female with a history of untreated mood disorder, hypertension, alcohol, and tobacco abuse presented to the emergency department (ED) with a three-month history of generalized body weakness. She also had a history of recurrent falls, difficulty walking, inadequate food and water intake, progressively worsening jaundice, and confusion which started about the same time. Her vital signs were normal; some of the significant physical examination findings were: sclera icterus, abdominal distension, bilateral pedal edema, hand tremors, rotary nystagmus, paraparesis, 1+ bilateral knee jerk, and absent bilateral ankle jerk. She had moderate hyponatremia, mild hypokalemia, deranged liver function test with a cholestatic pattern and transaminitis, hypoalbuminemia, elevated ammonia, lipase, in keeping with alcoholic liver disease and acute pancreatitis. In the ED, she received a normal saline infusion, and her serum sodium rose by just 6 mmol/L within the first 24 hours. She had drainage of her ascitic fluid and treatment with thiamine, folic acid, prednisone, lactulose, rifaximin, furosemide, spironolactone, and Ceftriaxone with improvement in clinical and laboratory abnormalities. Her lower extremity weakness persisted despite physical therapy, prompting neurologic evaluation. MRI of the lumbar spine showed an old compression fracture and lumbar spinal stenosis, while MRI brain findings were consistent with Osmotic demyelination. At the time of discharge to a rehabilitation facility, her serum sodium was 132 mmol/L, but her leg weakness persisted. Although rare, ODS can occur in the setting of moderate hyponatremia if there are additional risk factors that lower the threshold for demyelination.

Comparison of Drug Withdrawal Processes in the U.S. and Other Nations.

Medications have been withdrawn from as early as the 1900's in several countries due to a variety of reasons. Most drugs have been withdrawn due to safety, efficacy, manufacturing issues, or the toxicities they address. While safety and efficacy of each new drug is taken into account, so is the process of drug withdrawal. Worldwide each country has its own medical agency which have different approaches on drug discovery and method of removal from the market. This removal process is simpler in several nations while more prolonged in others. Nevertheless, we still don't know an effective method of drug removal from the market and therefore that is the focus of this paper. This paper explores the drug withdrawal process in several countries due to hepatic and cardiovascular toxicities using the WITHDRAWN database. It also summarizes and compares the drug removal processes in the U.S., Australia, UK, EU, and Canada. Consequently, there was no data or evidence that supported one country more favorable or rapid than the other. However, based on the results from drug withdrawal processes, it appeared the U.S., UK, and EU were most comparable. Meanwhile, Australia appeared to have the lengthiest process.

Biosafety Practices for In Vivo Viral-Mediated Gene Therapy in the Health Care Setting.

Introduction: Gene therapy encompasses a diverse array of genetically engineered products in biomedical research. As novel products continue to gain regulatory approval, institutions will be challenged by translating research processes into the clinical environment. This article will provide a summary of the 5 in vivo viral-based therapies that have been approved or are under review in the United States or European Union and discuss the development of biosafety handling practices in the clinical setting. Discussion: Commercially approved gene therapies utilize adeno-associated viral vectors, lentiviruses, and modified herpes simplex viruses for genetic manipulation. Health care personnel must understand the location of the genetic manipulation, ex vivo or in vivo, in order to develop safe work practices when handling the products. Occupational exposure to a viral agent could lead to risks of infection or acquired immunity. Institutions must merge biosafety and hazardous drug handling standards in order to develop safe handling procedures for clinical care. Conclusion: As biotechnology continues to advance, so will the challenges of incorporating novel therapies into the clinical setting. Health systems must educate themselves on the current recommendations and maintain competency of this evolving science to ensure the safety of patients, families, and staff in the clinical environment.

Anti-pathogenic potential of a classical ayurvedic Triphala formulation.

A classical ayurvedic polyherbal formulation namely Triphala was assessed for its anti-pathogenic potential against five different pathogenic bacteria. Virulence of four of them towards the model host Caenorhabditis elegans was attenuated (by 18-45%) owing to pre-treatment with Triphala (≤20 µg/ml). Triphala could also exert significant therapeutic effect on worms already infected with Chromobacterium violaceum, Serratia marcescens or Staphylococcus aureus. Prophylactic use of Triphala allowed worms to score 14-41% better survival in face of subsequent pathogen challenge. Repeated exposure to this formulation induced resistance in S. marcescens, but not in P. aeruginosa. It also exerted a post-extract effect (PEE) on three of the test pathogens. Triphala was able to modulate production of quorum sensing (QS)-regulated pigments in three of the multidrug-resistant gram-negative test bacteria. Haemolytic activity of S. aureus was heavily inhibited under the influence of this formulation. P. aeruginosa's lysozyme-susceptibility was found to increase by ~25-43% upon Triphala-pretreatment. These results validate therapeutic potential of one of the most widely used polyherbal ayurvedic formulations called Triphala.

Colloidally Stable Small Unilamellar Stearyl Amine Lipoplexes for Effective BMP-9 Gene Delivery to Stem Cells for Osteogenic Differentiation.

The biocompatibility of cationic liposomes has led to their clinical translation in gene delivery and their application apart from cancer to cardiovascular diseases, osteoporosis, metabolic diseases, and more. We have prepared PEGylated stearyl amine (pegSA) lipoplexes meticulously considering the physicochemical properties and formulation parameters to prepare single unilamellar vesicles (SUV) of < 100 nm size which retain their SUV nature upon complexation with pDNA rather than the conventional lipoplexes which show multilamellar nature. The developed PEGylated SA lipoplexes (pegSA lipoplexes) showed a lower N/P ratio (1.5) for BMP-9 gene complexation while maintaining the SUV character with a unique shape (square and triangular lipoplexes). Colloidal and pDNA complexation stability in the presence of electrolytes and serum indicates the suitability for intravenous administration for delivery of lipoplexes to bone marrow mesenchymal stem cells through sinusoidal vessels in bone marrow. Moreover, lower charge density of lipoplexes and low oxidative stress led to lower toxicity of lipoplexes to the C2C12 cells, NIH 3T3 cells, and erythrocytes. Transfection studies showed efficient gene delivery to C2C12 cells inducing osteogenic differentiation through BMP-9 expression as shown by enhanced calcium deposition in vitro, proving the potential of lipoplexes for bone regeneration. In vivo acute toxicity studies further demonstrated safety of the developed lipoplexes. Developed pegSA lipoplexes show potential for further in vivo preclinical evaluation to establish the proof of concept.

Hydroxyethyl substituted linear polyethylenimine for safe and efficient delivery of siRNA therapeutics.

Linear polyethylenimine (LPEI) has been well reported as a carrier for siRNA delivery. However, its applications are limited due to its highly ionized state at physiologic pH and the resultant charge mediated toxicity. The presence of ionizable secondary amines in LPE are responsible for its unique characteristics such as pH dependent solubility and positive charge. Therefore, modification of LPEI was carried out to obtain hydroxyethyl substituted LPEI with the degree of substitution ranging from 15% to 45%. The impact of modification on the physicochemical parameters of the polymer, i.e. buffer capacity, solubility, biocompatibility and stability, was evaluated. Surprisingly, despite the loss of ionizable amines, the substitution improved solubility, and even overcame the pH dependent solubility of LPEI. In addition, the conversion of secondary amines to less basic tertiary amines after substitution improved the buffer capacity, in the endosomal pH range, required for efficient endosomal escape. It also reduced erythrocyte aggregation, hemolytic potential and in vitro cytotoxicity. The in vitro studies showed enhanced cell uptake and mRNA knockdown efficiency. Thus, the proposed modification shows a simple approach to overcome the limitation of LPEI for siRNA delivery.

Osteocalcin, Vascular Calcification, and Atherosclerosis: A Systematic Review and Meta-analysis.

BACKGROUND: Osteocalcin (OC) is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations that the mechanism of vascular calcification resembles that of bone mineralisation. To date, studies have reported mixed results. This systematic review and meta-analysis aimed to identify any association between OC and vascular calcification and atherosclerosis. METHODS AND RESULTS: Databases were searched for original, peer reviewed human studies. A total of 1,453 articles were retrieved, of which 46 met the eligibility criteria. Overall 26 positive, 17 negative, and 29 neutral relationships were reported for assessments between OC (either concentration in blood, presence of OC-positive cells, or histological staining for OC) and extent of calcification or atherosclerosis. Studies that measured OC-positive cells or histological staining for OC reported positive relationships (11 studies). A higher percentage of Asian studies found a negative relationship (36%) in contrast to European studies (6%). Studies examining carboxylated and undercarboxylated forms of OC in the blood failed to report consistent results. The meta-analysis found no significant difference between OC concentration in the blood between patients with "atherosclerosis" and control (p = 0.13, n = 1,197). CONCLUSION: No definitive association was determined between OC and vascular calcification or atherosclerosis; however, the presence of OC-positive cells and histological staining had a consistent positive correlation with calcification or atherosclerosis. The review highlighted several themes, which may influence OC within differing populations leading to inconclusive results. Large, longitudinal studies are required to further current understanding of the clinical relevance of OC in vascular calcification and atherosclerosis.

Challenges in Dermal Delivery of Therapeutic Antimicrobial Protein and Peptides.

BACKGROUND: Protein and peptides in biological system form an important part of innate immune system and are being explored for potential use in various diseases as therapeutics. Importance of proteins and peptides as a new class of antimicrobial agents has boosted research in the field of biotechnology as potential alternative to antibiotic agents. OBJECTIVE: Protein and peptides antimicrobial as a therapeutic class are structurally diverse and exhibit potent activity against microbes by various mechanisms. However, they present formidable challenge in formulation due to requirement of specific spatial configuration for their activity and stability. Thus, encapsulation of these therapeutics in various nano-systems may sustain activity along with improvement in stability. METHOD: The article highlights the need for antimicrobial peptides in dermal infections along with discussion of mechanism of their action. It highlights challenges faced for dermal delivery and research carried out for their successful delivery using nano-systems. RESULTS: It is widely realized that these novel classes of therapeutic agents have tremendous market potential to emerge as an alternative to conventional antibiotic agents for combating issue of multidrug resistant microbial species. Research in their delivery aspects by use of current advances made in delivery systems through use of nanoconstructs offers much needed area for exploration and achieving success. CONCLUSION: As there is an urgent need for coming up with new therapeutic agents for encompassing the increased burden of microbial diseases in human population as well as their delivery challenges, research in field will give the much-needed strategic advantage against pathogenic organisms.

Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism.

Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3'UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & p<0.0001 for allele) and TG E33 (p = 0.0003 for E33TC p<0.0001 for E33CC& p<0.0001 for allele) SNPs between patients and controls. Patients had significantly decreased mRNA levels of both sCTLA4 (p = 0.0017) and flCTLA4 (p<0.0001) compared to controls. +49A/G and CT60 polymorphisms of CTLA4 were in moderate linkage disequilibrium. Logistic regression analysis indicated significant association of CT49A/G, CT60A/G and TG exon 33 polymorphisms with susceptibility to autoimmune hypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism.

Approaches and Recent Trends in Gene Delivery for Treatment of Atherosclerosis.

BACKGROUND: The development and progression of atherosclerosis is known to occur at a sluggish pace and the lesions remain concealed for a long duration before the factual situation of the complex atherosclerotic etiology affecting various organ gets apprehended. The root cause mainly involves an imbalance or malfunction of the cholesterol metabolizing pathway. The till date therapeutic alternatives include oral hypo-lipidemic agents along with advances made in biotechnology/tissue engineering and surgical procedures for management purpose. However, with the advent and upsurge of nanotech delivery systems, along with meticulous indulgence and identification of the causative genes in the etiology of disease have opened a new therapeutic area that has far reaching application potential for effective management of such chronic disease requiring lifelong therapy. METHODS: Various genes that have implication in atherosclerosis were reviewed along with research in delivery vectors that have been employed for gene therapeutics and hurdles in successful delivery were elaborated. Relevant patents are discussed systematically to clearly support and highlight the developments made. RESULTS: Patenting activity in the delivery of genes for atherosclerosis so far primarily covers use of viral vectors. With the identification of new targets, a list of candidate genes are available that can be potentially exploited for therapeutic purpose. Though the delivery of candidate genes using viral vectors has been well explored, the limitation of viral vectors have seized the much needed clinical success. Non-viral vectors can prove to be the key for conquering this limitations and offer a vast area for exploration for achieving an effective control and remission to the disease and increasing the assortment of patents as reviewed in this article. CONCLUSION: In view of the many limitations in employing viral vectors for delivery, designing non-viral vectors for successful delivery of therapeutic gene in atherosclerosis should be realized and focused for effective management of the disease.

Iso-petromyroxols: novel dihydroxylated tetrahydrofuran enantiomers from sea lamprey (Petromyzon marinus).

An enantiomeric pair of new fatty acid-derived hydroxylated tetrahydrofurans, here named iso-petromyroxols, were isolated from sea lamprey larvae-conditioned water. The relative configuration of iso-petromyroxol was elucidated with 1D and 2D NMR spectroscopic analyses. The ratio of enantiomers (er) in the natural sample was measured by chiral-HPLC-MS/MS to be ca. 3:1 of (-)- to (+)-antipodes.

Mucosal immunization: a review of strategies and challenges.

The vast majority of pathogens enter the human body via the mucosal surfaces of the gastrointestinal, respiratory, and urogenital tracts, where they initiate mucosal infections that lead to systemic infections. Despite strong evidence that a good mucosal immune response can effectively prevent systemic infection too, only a few mucosal vaccines are available due to their low efficiency. Most current immunization techniques involve systemic injection, but they are ineffective to induce immunization at a mucosal site. It is a great challenge to target a mucosal compartment that can induce protective immunity at mucosal sites as well as systemic sites. A better understanding of cellular and molecular factors involved in the regulation of mucosal immunity will aid in the design of safer mucosal vaccines that elicit the desired protective immunity against infectious diseases such as HIV. The development of mucosal vaccines, whether for prevention of infectious diseases or for immunotherapy, requires antigen delivery and adjuvant systems that can effectively present vaccine or immunotherapeutic antigens to the mucosal sites. In this review, we examine the mechanism of mucosal protection, induction of mucosal immune response, types of vaccines, current status of marketed vaccines, and novel strategies for protection against infections and for treatment of inflammatory disorders. Additionally, we offer perspectives on future challenges and research directions.