Search

While several lines of evidence suggest a protective role of T cells against disease associated with Dengue virus (DENV) infection, their potential contribution to immunopathology in the acute phase of DENV infection remains controversial, and it has been hypothesized that the more severe form of the disease (dengue hemorrhagic fever, DHF) is associated with altered T cell responses. To address this question, we determined the transcriptomic profiles of DENV-specific CD8+ T cells in a cohort of 40 hospitalized dengue patients with either a milder form of the disease (dengue fever, DF) or a more severe disease form (dengue hemorrhagic fever, DHF). We found multiple transcriptomic signatures, one associated with DENV-specific interferon-gamma responding cells and two other gene signatures, one specifically associated with the acute phase and the other with the early convalescent phase. Additionally, we found no differences in quantity and quality of DENV-specific CD8+ T cells based on disease severity. Taken together with previous findings that did not detect altered DENV-specific CD4 T cell responses, the current analysis argues against alteration in DENV-specific T cell responses as being a correlate of immunopathology.

Background: Germ cell tumours (GCT) are tumours arising from primordial germ cells. Gonadal and extragonadal GCT are infrequent in childhood occurring at a rate of 2.4 cases per million children accounting for 2-3 % of paediatric malignancies with most common subtype being a matured Teratoma. Case presentation: We present a case of a 10-year-old female child who presented to the emergency department of a tertiary care centre with complaints of cough with massive expectoration of blood of approximately 200 ml in quantity which on imaging revealed a left anterior mediastinal mass which was managed by left lateral thoracotomy with a non-anatomical left sided pulmonary lobectomy which on histopathology was diagnosed to be a case of mature teratoma. Conclusion: This case report describes a unique presentation of extra-gonadal mediastinal teratoma which presented as a rare complication with rupture into the left bronchus. It emphasizes caution and a high clinical suspicion is required in managing cases of varied presentations of teratomas.

Background: The definition of ectopic ureter is an abnormal opening of the ureter (single or duplex) that does not open in the trigonal region of the bladder. In 80% of these cases, ectopic ureter is associated with complete duplication. The upper moiety of a duplex kidney is usually the origin of a ectopic ureter in most of the cases. The opening of the ectopic ureteric in females can be anywhere from bladder neck to perineum with urethra, vagina, and vestibule. Duplex kidney, also known as duplex collecting system, is a common congenital urinary system anomaly with a morbidity of about 0.8–1%. We present a unique case of a completed duplicated system with ectopic ureter opening into the uterus leading to a non-functional associated upper renal moiety of the affected side which was managed by robotic assisted segmental nephrectomy. Case presentation: We present a case of 52-year- old lady who presented to urology outpatient department with complaints of sticky white perineal discharge through vaginum associated with left sided intermittent colicky flank pain who was diagnosed to have complete duplex left moiety with ectopic insertion of the upper moiety ureter into the vagina associated with non-functioning left upper renal moiety. She was managed by robotic assisted Left sided heminephrectomy with excision of left ectopic ureter. Conclusion: Our case report thus highlights the importance of adequate evaluation of a patient to determine the anatomy and the function of the kidney to decide for the definitive management of these patients with ectopic ureter and duplex kidneys.

Gossypiboma, a retained surgical sponge, is a rare complication following any surgical procedure and is primarily a result of human error. Such patients often have vague clinical presentations and the diagnosis often comes as a surprise and has serious medicolegal implications. We present a case of a 28-year-old female with a long-standing duration of 9 months with purulent discharge from the operated scar site of Lower segment caesarean section done 2 years back and then diagnosed to have a gossypiboma in the ureterovesical space causing structuring of the ipsilateral ureter which was successfully managed by Exploratory laparotomy with removal of the retained gossypiboma and right sided ureteric reimplantation.

Background: Academic trials are essential in investigating health research questions relevant to the society. Only a few leading research institutions in India have been engaged in academic trials. Thus, there is a need to understand what factors dampen the spirit of the academician in conducting academic clinical trials. Aims and Objectives: The aim of the study is to evaluate the investigator’s perception of obstacles to carrying out academic trials and to identify factors that will motivate investigators in conducting academic trials Materials and Methods: We conducted a prospective observational study in a tertiary care hospital for 6 months. Faculty members working in academic institutes were selected. A structured questionnaire was designed for the study and administered using google forms. Responses were taken on a Likert scale. Validity and reliability assessments were carried out. Mann-Whitney test was applied to assess differences between demographic groups. P 10 years of experience (P = 0.00001). Conclusion: Thus, to conclude the challenges faced by investigators were at multiple levels, most common being applying for research grants and making arrangements for the funds for payment towards participation or study-related injury. Faculty members with exposure to conducting clinical trials and with experience of more than 10 years had perceived a reduced degree of challenges.

Renal stones and their management forms bread and butter for a practising urologist. Percutaneous Cystolithotripsy (PCNL) forms the workhorse in the management of large renal stones with size greater than 2 cm. Many score predictors have been described to determine stone free rates and complications related to PCNL surgery.

Colovesical fistula is an improper connection between the urinary bladder and intestinal tract. Although there are many possible causes of colonovesical fistula, Chen et al. have classified them into five main classes: congenital, traumatic, tumor, inflammatory, and other. Intestinal diverticulitis accounts for 50-70% of cases in Western countries, and nearly all of them are related to colonic or bladder fistulas. Malignant tumors (20%) rank second in Western countries as the most common cause, which are situated largely in the large intestine. Other related tumours include bladder, cervical, ovarian and prostate cancers, and non-Hodgkin's lymphoma in the small intestine. The third most prevalent cause is Crohn's disease (10%), which occurs mainly in the ileum. "Other causes" include iatrogenic injury; trauma; foreign bodies in the intestinal tract; radiotherapy; chronic appendicitis

Abstract The preferred method for disease modeling using induced pluripotent stem cells (iPSCs) is to generate isogenic cell lines by correcting or introducing pathogenic mutations. Base editing enables the precise installation of point mutations at specific genomic locations without the need for deleterious double-strand breaks used in the CRISPR-Cas9 gene editing methods. We created a bulk population of iPSCs that homogeneously express ABE8e adenine base editor enzyme under a doxycycline-inducible expression system at the AAVS1 safe harbor locus. These cells enabled fast, efficient and inducible gene editing at targeted genomic regions, eliminating the need for single-cell cloning and screening to identify those with homozygous mutations. We could achieve multiplex genomic editing by creating homozygous mutations in very high efficiencies at four independent genomic loci simultaneously in AAVS1-iABE8e iPSCs, which is highly challenging with previously described methods. The inducible ABE8e expression system allows editing of the genes of interest within a specific time window, enabling temporal control of gene editing to study the cell or lineage-specific functions of genes and their molecular pathways. In summary, the inducible ABE8e system provides a fast, efficient and versatile gene-editing tool for disease modeling and functional genomic studies.

Urologists commonly make use of ureteral double J stents in endourology. If a DJ stent is forgotten to be removed, then complications happen in the form of encrustations, infection, migration, renal dysfunction and hydronephrosis. Ectopic pelvic Kidney is a relatively rare congenital anomaly caused by lack of ascent of the kidney. We report a very rare case of forgotten DJ stent in an ectopic kidney in a 55 years old patient with diabetes mellitus with history of left sided open pyelolithotomy done 21 months back. Redo open surgery was done to remove DJ stent along with stone removal.

Urethrocutaneous fistula (UCF) after hypospadias repair remain a frustrating Problem for all the practicing urologists. Furthermore, with the improvement in suture materials and surgical techniques, complications if they may arise also present with litigations for the urologist. We present a case of a 18 year old boy with 46 XY mixed gonadal dysgenesis who had undergone proximal hypospadias repair with Duckett’s tube urethroplasty with resultant complication of subcoronal urethrocutaneous fistula which failed first attempt at repair and resulted in two urethrocutaneous fistulas which was successfully managed by two stage Johanson’s urethroplasty.

The incidence of Lower urinary tract foreign body insertions is low. The motives for such insertion of a variety of objects are difficult to comprehend. We report a case of a 20-year-old male with multiple safety pins and broken incense sticks embedded inside his urethra which were successfully removed cystoscopically.

Background: Prostatic abscess is uncommon in adults and is infrequently noted in the paediatric population. Surgical drainage with adequate antibiotics is the current recommended management for prostatic abscess larger than 1 cm. However, it is still a topic debate that what should be the appropriate management of a prostatic abscess. Case presentation: Herein, we present the case of a 16-year-old young adolescent patient with a large prostate abscess without any systemic disease who was successfully managed with antibiotics only and surgical drainage was not required for this patient. Conclusion: Thus, we conclude that in a young adolescent patient with acute prostatic abscess, medical management with intravenous antibiotics deferring surgical drainage can be used an effective treatment option for management of this condition.

Horseshoe kidney is the most common genitourinary tract fusion abnormality at a frequency of 1 in 400-800 live births. PUJ obstruction is observed in up to one-third of these cases. The clinical presentation of the patients present will be either asymptomatic or may include stomach discomfort, persistent UTIs, and calculi. The PUJ obstruction is managed by surgery which can be carried out using a robotic, laparoscopic, or open technique. We hereby present a case of 16 hear old female with right sided PUJ obstruction due to high ureteric insertion in a horseshoe kidney which was effectively managed by open Anderson-Hynes Pyeloplasty.

Synchronous diagnosis of acute myeloid leukemia (AML) and multiple myeloma in chemotherapy-naïve patients is a rare event and poses a serious therapeutic challenge as it imparts a poor prognosis. We report a case of concurrent AML with multiple myeloma in a 44-year-old male along with a PUBMED-based research of previously reported similar cases in published literature.

Iatrogenic bladder injuries are a cause of morbidity in pelvic surgeries. Bladder perforation could be extraperitoneal or intra-peritoneal. Clinicaly, extraperitoneal bladder perforation is diagnosed by suprapubic pain, extravasation of urine into scrotum, perineum and thighs and difficulty in voiding whereas intraperitoneal bladder injury is diagnosed by signs of lower abdominal pain resembling acute abdomen. The diagnosis of bladder injury is confirmed by Computerised Cystography. The management of extraperitoneal bladder injury is catheter drainage while intraperitoneal bladder injury is managed by open repair. We present a case of Extraperitoneal iatrogenic bladder injury in a patient who underwent exploratory laparotomy for Appendicular perforation.

A 48-year-old female presented with complaints of right sided vague abdominal pain associated with abdominal lump.. Computed tomography revealed horseshoe kidney with Bosniak IIF cystic lesion arising from the interpolar region of right segment of the horseshoe kidney (HSK). In view of the persistent pain, patient underwent cyst excision. The final histopathology diagnosis was mucinous cystadenoma. On follow-up at 6 months post surgery, there was no recurrence. The histopathology is very unique and rare with only a few cases recorded in literature. The inner lining of the cyst wall composed of columnar epithelium secreting mucin and at some places by transitional epithelium. This indicates that the origin of the mucinous tumour was likely to be from a sequestration of the renal pelvic urothelium in the renal parenchyma.

The most frequent genitourinary fusion abnormality described in literature is horseshoe kidney. Horseshoe kidney because of its abnormal anatomy is linked to malrotations, fluctuating blood flow, high insertion of the ureter, a tendency to develop ureteropelvic junction (PUJ) obstruction in up to onethird of patients, and these are all presentations of this condition. One-third of the patients with horseshoe kidney present with either stone disease or PUJ obstruction. In our case report, we discuss the treatment of a 38-year-old male patient who had been complaining of abdominal pain for the past few years, was found to have a horseshoe kidney and presented to us in urosepsis due to gigantic large calculus in right segment of horseshoe kidney and acute renal failure which was managed initially on emergent basis by insertion of percutaneous nephrostomy tube into the right segment followed by 2 months later by open right sided nephropyelolithotomy. The patient was relieved of all his symptoms at 3rd month follow-up and resumed his daily activities.

Tuberculosis of the posterior elements is a rare and destructive form characterised by the destruction of the lamina, pedicle, or facet joints. Delay in clinical diagnosis and presentation is common because of poor visualisation of facet joints in X-rays. A 55-year-old male presented with back and left leg pain lasting for six months, accompanied by weakness in dorsiflexion of the left foot and ankle. Magnetic Resonance Imaging (MRI) revealed features suggestive of L4-L5 facetal arthritis on the left side, including marrow oedema, bone erosions, a posterior paraspinal abscess, and nerve root compression. The patient underwent posterior decompression and stabilisation, along with abscess drainage. The specimen was sent for histopathological examination, confirming the diagnosis of facetal joint tuberculosis. Antituberculous treatment was given for 12 months, that showed improved neurological status. This case is presented due to its rarity, highlighting the importance of considering facetal joint tuberculosis as a potential cause in cases of progressively increasing lower back pain, even in the absence of constitutional symptoms.

Congenital anomalies of Kidney and Urinary Tract (CAKUT) present with interesting challenges to a urologist in his practice. The incidence of CAKUT is 4.2 per 10,000 births. CAKUT are one of the major risk factors in adults requiring renal replacement therapy. Although children with CAKUT are often asymptomatic, CAKUT are estimated to be implicated in 30% to 60% of cases of childhood-onset chronic kidney disease (CKD) in different populations. We hereby present a rare case of a patient with Supernumerary Kidneys in which both bilateral native kidneys showed evidence of Pelvi-ureteric junction obstruction and ectopic pelvic kidney with normal function.

Objective The actual incidence and demographic profile of hematological malignancies are unknown in Bihar because of lack of population-based cancer registry (PBCR) data and specialized tertiary cancer center facilities. The objective of this study was to estimate the prevalence, clinico-hematological profile and subtyping of acute leukemia cases by retrospective medical records.

Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia with 2 variants: the primary form, which occurs de novo in patients with no previous history of multiple myeloma (MM), and the secondary form, which represents a leukemic transformation in patients with a previously recognized MM. Unlike myeloma, PCL typically follows an aggressive course, and the median age at presentation is usually above 50 years. In this report, we present a case of primary PCL that manifested at 19, an exceptionally rare occurrence.

Background and objectives: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, a newly emergent coronavirus, first recognized in Wuhan, China in December 2019. Early identification of laboratory indicators helps in distinguishing severe patients from mild to moderate counterparts and can facilitate medical interventions, thereby lowering the mortality rate. The present study was done to evaluate the role of hematological parameters and basic coagulation parameters in the assessment of the severity of COVID-19. Methods: This retrospective observational study was done at a tertiary care institute from May 2020 to May 2021. Hematological and coagulation profile was studied in 200 confirmed COVID-19 cases. Data related to age, gender, and clinical features were retrieved from patients’ records. Laboratory findings such as complete blood count neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and coagulation parameters in different categories were compared. Results: The majority of patients were males (59.5%) and with mild illness (52.5%). Moderate and severe illness was present in 30% and 17.5% of cases, respectively. The frequency of anemia, leucopenia, and thrombocytopenia was 62.5%, 6%, and 5.5%, respectively. Overall neutrophilia was seen in 40.5% of cases, whereas lymphopenia was seen in 39% of cases. Coagulation parameters were also much deranged in moderate and severe cases as compared to mild cases. Conclusion: The hematopoietic and hemostatic systems are significantly affected by COVID-19. Careful evaluation of laboratory parameters assists clinicians in formulating a tailored treatment approach and in predicting disease severity.

Hypocellular acute myeloid leukemia (AML) is an infrequent and challenging entity, and superinfection with coronavirus disease 2019 (COVID-19) could further complicate its diagnosis and management. It is characterized by low bone marrow cellularity, prominent cytopenias, and in many cases, clinically simulate aplastic anemia and hypoplastic myelodysplastic syndrome. We report a case of hypocellular AML-M2 in a 65-year-old male who was found to be COVID-19-positive. The cause of hypoplasia of bone marrow in such cases is still ambiguous and could be due to infiltration by blasts or co-infections. The cause of hypoplasia must be determined for proper management, which requires analysis of more such cases.

Drug-induced leukopenia is a diagnostic and therapeutic challenge. A detailed clinical history is a must to come to a right diagnosis. Certain drugs are known to cause bone marrow suppression, leukopenia, myeloid maturation arrest, and reactive promyelocyte proliferation. Here, we report an unusual case of vancomycin-induced maturation arrest with marked promyelocyte proliferation in a 47-year-old male patient who was being treated for novel coronavirus disease 2019 (COVID-19) infection. Most times, this reactive promyelocyte proliferation is confused with neoplastic promyelocytes, leading to incorrect diagnosis and management.

Background and aim: Cervical cancer is females' fourth most common cancer. A Pap smear is most commonly used for cervical cancer screening but has a low sensitivity. So, biomarkers can improve the diagnostic efficiency of screening programs. The aim of this study is to evaluate the sensitivity and specificity of cytology and biomarkers p53 and Bcl2 in detecting cervical neoplasia considering histopathological examination as the gold standard. Material and methods: It was a prospective hospital-based observational study. All cervical biopsies and surgically resected specimens received in the Histopathology laboratory of patients between 30-65 years were included. Results: One hundred and sixty patients who visited the Gynae-Oncology Outpatient department during the study period were enrolled. Out of these 10 cases were premalignant lesions and 97 cases of invasive carcinoma. Squamous cell carcinoma was the most common histological subtype of invasive cancer. Keratinizing Squamous cell carcinoma was the most common histological subtype of squamous cell carcinoma, and also Endocervical Adenocarcinoma was the most common histological subtype of Adenocarcinoma. Cytology had high specificity of 96.2% and low sensitivity of 59.8% in detecting cervical neoplasia. p53 staining on immunohistochemistry had a sensitivity of 77.6% and specificity of 90.6%. Bcl2 staining on IHC had the highest specificity of 100% and sensitivity of 48%. Conclusions: Combined use of cytology and biomarkers analysis increases the chances of detecting cervical cancer at early stages than using any single screening test. It will help in reducing patient morbidity and mortality.

COVID-19 continues to cause an increase in the number of cases and deaths worldwide. Due to the ever-mutating nature of the virus, frequent vaccination against COVID-19 is anticipated. Most of the approved SARS-CoV-2 vaccines are administered using the conventional intramuscular route, causing vaccine hesitancy. Thus, there is a need for an effective, non-invasive vaccination strategy against COVID-19. This study evaluated the synergistic effects of a subunit microparticulate vaccine delivered using microneedles. The microparticles encapsulated a highly immunogenic subunit protein of the SARS-CoV-2 virus, such as the spike protein’s receptor binding domain (RBD). Adjuvants were also incorporated to enhance the spike RBD-specific immune response. Our vaccination study reveals that a microneedle-based vaccine delivering these microparticles induced spike RBD-specific IgM, IgG, IgG1, IgG2a, and IgA antibodies. The vaccine also generated high levels of CD4+ and CD8a+ molecules in the secondary lymphoid organs. Overall, dissolving microneedles delivery spike RBD antigen in microparticulate form induced a robust immune response, paving the way for an alternative self-administrable, non-invasive vaccination strategy against COVID-19.

Introduction: Long-term repercussions of Coronavirus Disease-2019 (COVID-19) on antimicrobial resistance have been raised as a grave concern due to the rampant use of antibiotics in the management of COVID-19. As per meta-analysis, the prevalence of antibiotic prescribing was 74.6% which was significantly higher than the estimated prevalence of bacterial co-infection. World Health Organisation (WHO) recommended that antibiotic therapy should not be used in patients with mild/moderate COVID-19 unless there is any bacterial suspicion. Also, the guidelines laid down by the Ministry of Health and Family Welfare, Government of India, does not recommend systematic empiric antibiotic therapy in patients hospitalised with COVID-19. Despite not being recommended, antimicrobials are still given in clinical practice. Aim: To analyse prescriptions for antimicrobials and to identify potential predictors for antibiotic prescription. Materials and Methods: A retrospective observational study was conducted at a tertiary care teaching Institute, Nagpur, Maharashtra, India. Data (demographic profile, co-morbidities, disease category, prescribed antimicrobials, laboratory investigations, and duration of hospital stay) were collected from case files of 184 patients with laboratory-confirmed Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection. These patients were admitted in the institute from January 2021 to May 2021. Logistic regression was used to analyse factors associated with the empirical use of antimicrobial agents. Results: A total of 184 case files were analysed. The mean age of patients was 55.84±15.72 years, with a male preponderance (70.10%). Among antimicrobials, antivirals were prescribed in 159 (86.41%) patients, and antibiotics in 152 patients (82.6%). Antivirals prescribed include Remdesivir [109 (68.55%)] and Favipiravir [70 (44.02%)]. Ceftriaxone was found to be the highest prescribed antibiotic, with a median duration of administration of six days. An association was found between disease severity and CRP level with antibiotic prescription. On multivariable analysis, the odds of receiving antibiotics were 6.7 times higher in patients with severe disease. Conclusion: More than 80% of COVID-19 patients received antibiotics. Duration of hospital stay was similar among patients whether they received antibiotics or not. Disease severity and raised CRP level were strong predictors for prescribing antibiotics for COVID-19.

Several anatomic factors like midline septum, lateral peridural membrane and epidural fat prevent dorsal migration of disc fragment. Hence, dorsal epidural migration of lumbar disc has a rare occurrence. It has a propensity to present with cauda equina syndrome. Epidural disc fragments mimic benign masses and hence poses a diagnostic challenge. The prognosis is good compared to other types of disc prolapse when surgical decompression is done early. A 45-year-old male labourer presented with chronic lower back pain with recent onset of motor weakness in right lower limb and bladder disturbance. Magnetic Resonance Imaging (MRI) showed a huge sequestrated L4-L5 disc. Emergency decompression with laminectomy was done and a large fragment of sequestrated disc found in posterior epidural space was removed. Symptoms improved dramatically following surgery within 10 days. Awareness about this rare disc prolapse is important for timely diagnosis and management of it.

Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis and pneumonia in children ages five years and below. Recent outbreaks of the virus have proven that RSV remains a severe burden on healthcare services. Thus, a vaccine for RSV is a need of the hour. Research on novel vaccine delivery systems for infectious diseases such as RSV can pave the road to more vaccine candidates. Among many novel vaccine delivery systems, a combined system with polymeric nanoparticles loaded in dissolving microneedles holds a lot of potential. In this study, the virus-like particles of the RSV fusion protein (F-VLP) were encapsulated in poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). These NPs were then loaded into dissolving microneedles (MNs) composed of hyaluronic acid and trehalose. To test the in vivo immunogenicity of the nanoparticle-loaded microneedles, Swiss Webster mice were immunized with the F-VLP NPs, both with and without adjuvant monophosphoryl lipid A (MPL) NPs loaded in the MN. The mice immunized with the F-VLP NP + MPL NP MN showed high immunoglobulin (IgG and IgG2a) levels both in the serum and lung homogenates. A subsequent analysis of lung homogenates post-RSV challenge revealed high IgA, indicating the generation of a mucosal immune response upon intradermal immunization. A flowcytometry analysis showed high CD8+ and CD4+ expression in the lymph nodes and spleens of the F-VLP NP + MPL NP MN-immunized mice. Thus, our vaccine elicited a robust humoral and cellular immune response in vivo. Therefore, PLGA nanoparticles loaded in dissolving microneedles could be a suitable novel delivery system for RSV vaccines.

Although the global Zika epidemic in 2015–16 fueled vaccine development efforts, there is no approved Zika vaccine or treatment available to date. Current vaccine platforms in clinical trials are administered via either subcutaneous or intramuscular injections, which are painful and decrease compliance. Therefore, in the present study, we explored Zika vaccine microparticles (MPs)-loaded dissolving microneedles (MNs) with adjuvant MPs encapsulating Alhydrogel® and MPL-A® administered via the transdermal route as a pain-free vaccine strategy. We characterized the MNs for needle length, pore formation, and dissolvability when applied to murine skin. Further, we evaluated the in vivo efficacy of vaccine MPs-loaded MNs with or without adjuvants by measuring the immune response after transdermal immunization. The vaccine MPs-loaded dissolving MNs with adjuvants induced significant IgG, IgG1, and IgG2a titers in immunized mice compared to the untreated control group. After the dosing regimen, the animals were challenged with Zika virus, monitored for seven days, and sacrificed to collect spleen and lymph nodes. The lymphocytes and splenocytes from the immunized mice showed significant expressions of helper (CD4) and cytotoxic (CD8a) cell surface markers compared to the control group. Thus, this study puts forth a ‘proof-of-concept’ for a pain-free transdermal vaccine strategy against Zika.

Background: The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Methods: We investigated immune responses in adult individuals pre and 8 months post BCG vaccination. We specifically determined changes in gene expression, cell subset composition, DNA methylome, and the TCR repertoire induced in PBMCs and CD4 memory T cells associated with antigen stimulation by either BCG or a Mycobacterium tuberculosis (Mtb)-derived peptide pool. Findings: Following BCG vaccination, we observed increased frequencies of CCR6+ CD4 T cells, which includes both Th1* (CXCR3+CCR6+) and Th17 subsets, and mucosal associated invariant T cells (MAITs). A large number of immune response genes and pathways were upregulated post BCG vaccination with similar patterns observed in both PBMCs and memory CD4 T cells, thus suggesting a substantial role for CD4 T cells in the cellular response to BCG. These upregulated genes and associated pathways were also reflected in the DNA methylome. We described both qualitative and quantitative changes in the BCG-specific TCR repertoire post vaccination, and importantly found evidence for similar TCR repertoires across different subjects. Interpretation: The immune signatures defined herein can be used to track and further characterize immune responses induced by BCG, and can serve as reference for benchmarking novel vaccination strategies.

This ‘proof-of-concept’ study aimed to test the microparticulate vaccine delivery system and a transdermal vaccine administration strategy using dissolving microneedles (MN). For this purpose, we formulated poly(lactic-co-glycolic) acid (PLGA) microparticles (MP) encapsulating the inactivated canine coronavirus (iCCoV), as a model antigen, along with adjuvant MP encapsulating Alhydrogel® and AddaVax. We characterized the vaccine MP for size, surface charge, morphology, and encapsulation efficiency. Further, we evaluated the in vitro immunogenicity, cytotoxicity, and antigen-presentation of vaccine/adjuvant MP in murine dendritic cells (DCs). Additionally, we tested the in vivo immunogenicity of the MP vaccine in mice through MN administration. We evaluated the serum IgG, IgA, IgG1, and IgG2a responses using an enzyme-linked immunosorbent assay. The results indicate that the particulate form of the vaccine is more immunogenic than the antigen suspension in vitro. We found the vaccine/adjuvant MP to be non-cytotoxic to DCs. The expression of antigen-presenting molecules, MHC I/II, and their costimulatory molecules, CD80/40, increased with the addition of the adjuvants. Moreover, the results suggest that the MP vaccine is cross presented by the DCs. In vivo, the adjuvanted MP vaccine induced increased antibody levels in mice following vaccination and will further be assessed for its cell-mediated responses.

Chronic Lymphocytic Leukaemia (CLL) is commonly associated with autoimmune cytopenias but CLL presenting with pancytopenia is a rare occurrence. Here, we present a case of 56-year-old male patient, who presented with pallor, mild hepatosplenomegaly, right-sided pleural effusion in chest x-ray, pancytopenia and his bone marrow showed infiltration by mature appearing lymphoid cells making a diagnosis of CLL. Despite the frequency of these immune mediated cytopenia, only few cases of pancytopenia have been described so far to the best of our knowledge. Hence, to emphasise the rarity of such haematological coincidence we are presenting this case report. CLL generally presents with persistent absolute lymphocytosis on peripheral smear with an absolute monoclonal lymphocyte count of more than 5000/cumm. There is a common association with Autoimmune Haemolytic Anaemia (AIHA) and Immune Thrombocytopenia (ITP) and the association is called as Evan’s syndrome. Its pathogenesis is associated with autoimmune process. AIHA, ITP, and Pure Red Cell Aplasia (PRCA) are commonly associated complications seen in CLL. The pathogenesis of AIHA and ITP are antibody this inplace of the reactions and abnormal T cell activity is noted in the pathogenesis of PRCA. Despite of the frequency of these immune mediated cytopenias noted in CLL, bone marrow was seen to be hypercellular in most of the cases and marrow hypoplasia have been reported in only 2 cases reported in literature so far. In the present case, although pancytopenia was present on peripheral blood smear examination but bone marrow was hypercellular for age with diffuse infiltration by monoclonal mature appearing lymphoid cells which makes this case all the more interesting. Despite repeated blood transfusions,antiviral drug Tenofovir and aggressive supportive measures for 6 months, he developed right-sided pleural effusion and succumbed to his illness.

Abstract Background Pseudomonas aeruginosa have been delineated for its disreputable charisma in nosocomial infections leading to pulmonary pneumonia. The recent developments in multi-drug resistance accelerate the need of alternative antibacterial strategies. In this study we analysed the efficacy of quorum quenching mediated bacterial silencing in effective immunological clearance upon pulmonary infected rat models. Results Quorum sensing inhibitor was extracted from Solanum torvum which is a native plant in Kerala, India. The in vitro pilot studies upon Pseudomonas aeruginosa strain jb07 revealed the ability of Solanum torvum root extract (STRE) to successfully inhibit quorum sensing controlled virulent factors such as chromogenesis and biofilm formation; though the bacterial growth was unaffected. In vivo analysis upon Sprague Dawley rats shown the potential of STRE in aiding successful bacterial clearance where in cent percentage of survival was evident that compared with untreated group. Subjects treated with STRE possessed natural immunological response with inflammation, MNC infiltration and BALT (bronchus associated lymphoid tissue) hyperplasia unlike the Ciprofloxacin treated comparative group. Conclusions The observations of this study suggests that STRE is not having any bactericidal activity rather its silencing the infectant in a system which in turn disables the virulence of bacteria and remain attenuated; therefore immune system get adequate time for successful countermeasures.

Introduction: Since time immemorial man has tried to improve upon teaching methods so that students can become more proficient. Biopsy slides of pathology have been difficult for medical students to understand and comprehend since a long time. The introduction of projection microscope for teaching biopsy slides would go a long way in simplifying the whole process. Methodology: The authors compared the two teaching methods for identifying pathologic lesion in biopsy slides. Ninety nine fourth semester undergraduate students were divided into two groups with group A having fifty students and group B having forty nine students. The period of our study of four months was divided into two, two month period. In the first two months group B was made the test group and taught biopsy slides using projection microscope and group A was made control group and was taught by conventional method (atlas, chalk and board). To avoid any form of bias, in the second two months their roles were reversed so that group A was made the test group and group B was made the control group. Result: After each two month OSPE was held and marks recorded. At the end of four month period a survey was taken from students and faculty in a feedback form based on Likert scale. In this survey it was found that ninety percent (90%) of the students and faculty were of the view that visual aided method of teaching was superior to conventional method of teaching biopsy slides. In the OSPE the group which underwent visual method of teaching scored higher than the group which underwent conventional method of teaching even after swapping of their roles after two months. Discussion: Teaching tools using two or more senses is superior to teaching with one sense only. This is specially true while using visual and auditory method of teaching which accounts for 88% of our learning. Here we have made good use of visual aid in form of projection microscope to teach and explain the morphologic features of pathologic lesion in a biopsy slide.

Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artifacts and thus ignored in data acquisition and analysis, are the result of biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell-monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be re-visited.

Among the four types of influenza viruses, the influenza A strains and their subtypes have been responsible for causing worldwide pandemics and seasonal epidemics [...]

Primary Ewing Sarcoma of the cranial bone is rare, contributing to only 1% of all Ewing Sarcomas. Primary cranial Ewing Sarcoma occurs most commonly in temporal bone followed by parietal and occipital bones. Sphenoid bone is less commonly involved. We report a case of Ewing Sarcoma of the sphenoid bone with intra-cranial extension in a 20-month-old boy. On CT scan a provisional diagnosis of rhabdomyosarcoma was made. Fine Needle Aspiration Cytology (FNAC) and histopathological examination of core needle biopsy showed small round cell tumour. On Immunohistochemistry (IHC), CD99 (MIC2) and FLI 1 were strongly positive and final diagnosis of Ewing Sarcoma was made. Considering the rarity of this unusual site, we report a case of primary Ewing Sarcoma arising in the sphenoid bone with erosion of adjacent bones and intra-cranial extension.

G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways.

Objective: To explore biofertilizing efficiency of seaweed liquid extracts of brown alga Sargassum wightii (S. wightii) on growth, biochemical and yield parameters of Cyamopsis tetragonoloba (C. tetragonoloba). Methods: Seaweeds were made to coarse powder and stock solution was prepared. Different concentrations such as 0.5%, 1.0%, 1.5%, 2.0%, 2.5% and 5.0% were prepared and given as foliar spray. Results: Seaweed Liquid Extract (SLE) at low concentration (1.5%) exhibited promoting effect on growth and yield parameters. Differential responses in the content of photosynthetic pigments, protein, reducing sugar, ascorbic acid and in the activity of nitrate reductase were also observed in the leaves of SLE treated seedlings when compared to untreated seedlings. Higher concentrations (above 1.5%) of SLE were found to show inhibitory effect. Conclusion: The presence of micro and macro nutrients, vitamins, growth hormones and other constituents in the seaweed extract might be very much useful to the crops but their level should be appropriate to enhance growth and productivity. It may be concluded that liquid seaweed extracts could serve as cost effective eco-friendly product for sustainable agriculture.

Actinomycosis in the pelvic region is an uncommon diagnosis. This infection is caused by Actinomyces israelii, a gram-positive anaerobic saprophyte bacterium that is a normal inhabitant of the upper intestinal tract in humans. Pelvic actinomycosis is difficult to diagnose pre-operatively and is diagnosed, in most cases, accidentally. Actinomycosis can mimic pelvic and abdominal malignancies. A case report of a 35-year-old female patient with a fixed pelvic mass is presented. Despite the broad use of tumor markers, sonography and computerized tomography, the differentiation between benign and malignant pelvic masses is still a clinical challenge. Accurate differential diagnosis is necessary because the treatment strategies vary greatly. A case of actinomycotic inflammatory disease, which was misdiagnosed as an advanced ovarian cancer, is reported.

We report a case of Lipoblastoma in a 4-year-old boy along with a brief review of literature. Lipoblastomas are rare benign tumors that arise from embryonic white fat. These lesions exhibit a wide range of cellular differentiation and maturation. A range of differentiation from unvacuolated spindle cells within the myxoid matrix to increasingly larger and more vacuolated cells to the mature adipocyte, can be noted at high power. These lesions are typically asymptomatic and most cases are diagnosed within the first decade of life. This case report tries to describe the importance of differentiating Lipoblastoma from myxoid Liposarcoma. Lipoblastomas when followed, gradually mature, with the disappearance of the spindle and myxoid elements.

Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development.MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design.We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p

Chronic damage and repair of the bronchial epithelium are features of asthma. We have previously reported that ex vivo stimulation of normal bronchial epithelial cells with epidermal growth factor (EGF), a key factor of epithelial repair, enhances the mechanisms of neutrophil accumulation, thereby promoting neutrophil defences during acute injury but potentially enhancing inflammation in chronic airway diseases. We have now sought to (i) determine whether this EGF-dependent pro-neutrophil activity is increased in asthma, where EGF and its epithelial receptor are over-expressed, and (ii) elucidate some of the mechanisms underlying this asthmatic epithelial-neutrophil interaction. Primary bronchial epithelial cells (PBEC) from healthy subjects, mild asthmatics and moderate-to-severe asthmatics (Mod/Sev) were stimulated with EGF, a model that mimics a repairing epithelium. Conditioned culture media (EGF-CM) were assessed for neutrophil chemotactic and anti-apoptotic activities and inflammatory mediator production. EGF induced the epithelium to produce soluble mediators with neutrophil chemotactic (p

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease.

Abstract Introduction The most common cause of parotid fistula is trauma, followed by malignancy, operative complications (parotidectomy or rhytidectomy) and infection. Acute suppurative parotitis can rarely produce parotid fistula. There are various treatment options available, however it is necessary to standardize the treatment according to the duration of history and the patient's general condition. Case report A 13-year-old Indo-Caucasian girl presented to us with a two-year history of clear watery discharge from a wound just above and behind the angle of her right jaw. A diagnosis of salivary (parotid) fistula was made based on clinical examination and investigations. The parotid fistula was successfully managed. Conclusion Parotid fistula secondary to suppurative parotitis is rare and difficult to manage successfully. Meticulous dissection, complete excision of the fistulous tract with closure of the parotid fascia and layered closure of the incision followed by application of a post-operative pressure bandage, anticholinergic agents and antibiotics contribute significantly to the successful management of this difficult clinical condition.