A review on RNA interference studies in Anophelines to reveal candidate genes for malaria transmission blocking vaccine.

Malaria is a major public health concern. The development of parasite-based vaccine RTS/AS01 has some therapeutic value but its lower efficacy is one of the major limitations. Mosquito-based transmission-blocking vaccines could have a higher potential for parasite inhibition within the mosquitoes. Several genes of mosquito midgut, salivary gland, hemolymph, etc. get activate in response to the Plasmodium-infected blood and helps in parasite invasion directly or indirectly inside the mosquito. The studies of such genes provided a new insight into developing the more efficient vaccines. In the field of malaria genetics research, RNAi has become an innovative strategy used to identify mosquito candidate genes for transmission-blocking vaccines. This review targeted the gene studies that have been conducted in the period 2000-2023 in different malaria vectors against different malarial parasites using the RNAi approach to reveal mosquito novel gene candidates for vaccine development.

Leptospirosis Associated Digital Gangrene of Lower Extremities: Two Cases and Review of Literature.

BACKGROUND: Leptospirosis is the most common zoonotic illness worldwide, caused by pathogenic spirochete bacteria called Leptospirosis. It is clinically presented with mild to moderate in most cases. However, sometimes, the course may be severe with multiorgan dysfunction. CASE PRESENTATION: We present two rare cases of Leptospirosis with peripheral dry gangrene of the lower extremities. A 25-year-old male, farmer by occupation without any significant past medical history had been diagnosed with a case of Leptospirosis that complicated to digital gangrene on 15 days of illness during hospitalization. Another 21-year-old male student was admitted for leptospirosis and developed digital gangrene on 19 days of illness. All clinical findings were resolved on the steroid. CONCLUSION: Apart from a high index of suspicion and awareness of unusual manifestations, serology plays a vital role in making an accurate and quick diagnosis to initiate appropriate therapy.

Role of HLA alleles polymorphism in systemic lupus erythematosus: A prospective study from North India.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder and has complex etiopathogenesis. The most appropriate hypothesis states that genetic susceptibility in the presence of environmental risk factors predisposes to SLE. HLA class II alleles are critical to immune response and are highly polymorphic. Various alleles in HLA-DR and -DQ regions were analyzed in SLE patients and healthy controls to see their role in susceptibility or protection to SLE. Materials and Methods: This was a prospective observational study, in which a total of 100 SLE patients and 100 controls were analyzed. HLA typing was done by polymerase chain reaction (PCR)-sequence-specific oligonucleotide (SSO) method (SSO probe). Results: DRß1*0301 was significantly increased in SLE patients when compared to controls and had the highest odds ratio. Other risk factor alleles found to be increased were DRß1*0701, DQß1*0202, and DQß1*0301, which had a significant positive association with SLE, suggesting their role in susceptibility to SLE. In contrast, DRß1*0401, DRß1*1401, DRß1*1404, DRß1*1501, DQß1*0501, and DQα1*0201 showed statistically significant reduction in SLE patients, while these were much more common in controls, suggesting their protective role. Conclusion: This study is only the second study in patients from North India and it determines the role of DRß1*0301, DRß1*0701, DQß1*0202, and DQß1*0301 alleles as risk factors in SLE patients.

Mosquito gene targeted RNAi studies for vector control.

Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.

Transovarial transmission of mosquito-borne viruses: a systematic review.

Background: A number of mosquito-borne viruses (MBVs), such as dengue virus (DENV), zika virus (ZIKV), chikungunya (CHIKV), West Nile virus (WNV), and yellow fever virus (YFV) exert adverse health impacts on the global population. Aedes aegypti and Aedes albopictus are the prime vectors responsible for the transmission of these viruses. The viruses have acquired a number of routes for successful transmission, including horizontal and vertical transmission. Transovarial transmission is a subset/type of vertical transmission adopted by mosquitoes for the transmission of viruses from females to their offspring through eggs/ovaries. It provides a mechanism for these MBVs to persist and maintain their lineage during adverse climatic conditions of extremely hot and cold temperatures, during the dry season, or in the absence of susceptible vertebrate host when horizontal transmission is not possible. Methods: The publications discussed in this systematic review were searched for using the PubMed, Scopus, and Web of Science databases, and websites such as those of the World Health Organization (WHO) and the European Centre for Disease Prevention and Control, using the search terms "transovarial transmission" and "mosquito-borne viruses" from 16 May 2023 to 20 September 2023. Results: A total of 2,391 articles were searched, of which 123 were chosen for full text evaluation, and 60 were then included in the study after screening and removing duplicates. Conclusion: The present systematic review focuses on understanding the above diseases, their pathogenesis, epidemiology and host-parasite interactions. The factors affecting transovarial transmission, potential implications, mosquito antiviral defense mechanism, and the control strategies for these mosquito-borne viral diseases (MBVDs) are also be included in this review.

Clinicopathological Profile of the von Willebrand Disease in a Tertiary Care Centre in Varanasi.

Objective The von Willebrand disease (vWD) is one of the most common inherited bleeding disorders in India; however, the diagnostic tests and its interpretation require specialized laboratory and personnel which are not readily available in the eastern part of North India. The purpose of this study is to estimate the relative prevalence of vWD and study the clinical and laboratory features including advanced diagnostic tests. Methods All patients referred to the pathology department for evaluation of bleeding were evaluated for vWD during a period of 4 years. Clinical and laboratory features were analyzed and reported. Results A total of 1,126 cases of bleeding manifestations were evaluated, and 237 cases of inherited bleeding disorders were diagnosed; vWD was diagnosed in 38 (16%) of these 237 cases. Advanced diagnostic tests were done in all of these cases. Conclusion The vWD is among the most common inherited bleeding disorders in the country, second only to hemophilia A. Type-1 vWD was the most frequent with 25 cases (65.7%), followed by type-2N with 7 cases (18.4%).

Emergence of SARS-CoV-2 New Variants and Their Clinical Significance.

COVID-19 is a respiration-related disease caused by SARS-CoV-2 and was identified in China's Wuhan city. More than 223 countries are affected by the disease worldwide. The new variants of the COVID-19 virus are causing problems, from average to life-threatening pneumonia and acute respiratory distress syndrome (ARDS). Presently, there are 170 vaccine candidates, out of which 10 have been approved by the WHO for vaccination, such as Ad26.COV2.S, Pfizer/BioNTech, COVISHIELD, Covovax, Moderna, KoviVac, and some other vaccines to combat the deadly SARS-CoV-2 infection. From all these vaccines, Pfizer/BioNTech and Moderna are showing the highest efficacy against COVID-19. These vaccines are highly efficient against COVID-19 disease, but their potentiality against new variants remains a question. COVID-19 vaccines are highly effective at preventing severe illnesses, hospitalizations, and death. The antibodies elicited by earlier infection or vaccination are the key for possible protection against SARS-CoV-2. The problem has been exacerbated by new information from Africa on the origins of the novel contagious SARS-CoV-2 strain. These new strains occur due to unique mutations in the spike protein, which modify SARS-CoV-2 transmission and infection capabilities, limiting the efficacy of the COVID-19 vaccination. Hence, there is a need to find a potential vaccine against it.

Zika virus vertical transmission in mosquitoes: A less understood mechanism.

Zika virus disease is a great concern in different parts of the world, and it has become a Public Health Emergency of International Concern. The global pandemic of ZIKV in 2015 prompted concern among scientific community. Zika is a flavivirus of the family Flaviviridae transmitted by mosquitoes. Natural vertical transmission is an ecological strategy that arboviruses adopt to ensure their survival inside the mosquito vector during harsh conditions or interepidemic periods when horizontal transmission is difficult. ZIKV is vertically transmitted from infected females to its offspring. This review has concluded various studies regarding the vertical transmission ability of different mosquito species for ZIKV. Previously Aedes aegypti was considered to be a major vector, however Aedes albopictus and Culex quinquifasciatus are discovered to have the similar vertical transmission potential. Different studies shown that natural vertical transmission has been detected in mosquito species which are not implicated as possible vectors. It leads to the possibility that many other mosquito species may be potential ZIKV vectors.

Serum complements and immunoglobulin profiles in systemic lupus erythematosus patients: An observational study at a teaching hospital.

Context: Serum complement proteins and autoantibodies play an important role in the pathogenesis and diagnosis of systemic lupus erythematosus (SLE). Abnormalities in various immunoglobulin levels are described in patients of SLE. Aims: To study the spectrum of clinical manifestations and measure the serum levels of complement C3, complement C4, autoantibodies and immunoglobulin G (IgG) in patients of SLE and compare with healthy controls. Settings and Design: The present study is a prospective hospital-based observational study conducted between May 2014 and December 2018. Statistical Analysis Used: Unpaired t-test was used to compare the mean values between the SLE patients and healthy controls. Material and Methods: A total of 100 cases of SLE and 100 healthy controls were included in the study. The clinical data were retrieved. Serum antinuclear antibody, anti-ds DNA antibody, and anti-Smith antibody levels, and complements C3, C4 and IgG were measured. Results: Arthritis (89%) and anaemia (65%) were two common clinical presentations. The low complement C3 levels and C4 were detected in 64 and 62% of the SLE patients. Serum IgG was increased in 41% of the patients. A reduced level of IgG was detected in 6% of the patients. Conclusion: Primary care physicians should be aware of the clinical and serological manifestations of SLE as early detection will reduce end-organ damage. Autoantibody testing and complement testing should be done in all suspected cases. This study showed a significantly reduced C3 and C4 and elevated IgG in many cases of SLE as compared to control. Hypogammaglobulinemia was also present in a minority of the cases.

Correction: Homology modeling and molecular dynamics simulation study of beta carbonic anhydrase of Ascaris lumbricoides in Yadav and Khandelwal, 2019.

[This corrects the article on p. 572 in vol. 15, PMID: 31719767.].

Ocular cysticercosis at a teaching hospital in Northern India.

BACKGROUND: Ocular cysticercosis (OC) is common in tropical countries. This study aimed to analyze the clinical presentation patterns, management and treatment outcomes of OC cases seen at a teaching hospital in North India. METHODS: This study took place between March 2014 and February 2019. A total of 36 patients with OC were analyzed to determine clinical presentation and outcomes. RESULTS: Of the 36 patients, 13 (36.11%) were male and 23 (63.89%) were female. The most frequently affected age group was 10-29 years (n = 22; 61.11%). All of the patients had unilateral lesions, with involvement of the left eye in 22 (61.11%) and the right in 14 (38.89%). The majority of cases were isolated to the ocular region; however, five (13.89%) demonstrated neural involvement as well. In terms of cyst location, 15 (41.67%) were orbital, 13 (36.11%) were subconjunctival and four each (11.11%) were intraocular or on the eyelid. The most common clinical presentations were subconjunctival masses or proptosis in 13 each (36.11%) and periorbital swelling in 12 (33.33%). Most patients received medical treatment (n - 23; 63.89%), while the others required surgical excision. Recurrence was noted in seven patients (19.44%), of which three underwent surgery while the rest were treated medically. Two patients (5.56%) developed phthisis. CONCLUSIONS: In this study, OC cysts were more often orbital or subconjunctival compared to findings reported from Western countries. In addition, a female preponderance was noted in contrast to previously reported findings. Advanced radioimaging is crucial to ensure early diagnosis and treatment.

Epithelial-myoepithelial carcinoma at the base of the tongue presented with metastatic disease in the absence of myoepithelial anaplasia.

Epithelial-myoepithelial carcinoma (EMC) is a biphasic low-grade malignant tumor that shows ductal structures lined by the ductal cells with surrounding myoepithelial cells. EMC is most commonly reported in the parotid gland followed by other major and minor salivary glands. EMC of the tongue is an extremely uncommon tumor, with only five previously published case reports. We herein report the sixth case of EMC of the tongue. A 40-year-old female who had throat pain, dysphagia, and right earache for 3 years showed a 4 cm × 4 cm nodular tumor at the base of her tongue. Histopathological and immunohistochemical features were diagnostic of EMC with cervical lymph node metastasis. The metastatic behavior of EMC of the tongue in the absence of myoepithelial anaplasia or high-grade histological features is unusual and reported in this case report for the first time.

Homology modeling and molecular dynamics dimulation study of ß carbonic anhydrase of Ascaris lumbricoides.

Ascaris lumbricoides is the prevalent parasite causing ascariasis by infecting the human alimentary tract. This is common in the jejunum of small intestine. Therefore, it is of interest to describe the target protein ß Carbonic Anhydrase involved in Ascariasis. Carbonic anhydrase (CAs, the metallo enzymes) is encoded by six evolutionary divergent gene families α, ß,γ, δ, ζ, and η, which contain zinc ion in their catalytic active site. ß-CA is found in plants, algae, fungi, bacteria, protozoans, arthropods, and nematodes and completely absent in vertebrate genomes. The absence of ß-CA protein in vertebrate makes the enzyme an important target for inhibitory studies against helminthic infection. The sequence to function related information and 3D structure data for ß-CA of Ascaris lumbricoides is not available. Hence, we modeled the 3D structure (using PRIME) for the molecular dynamics and simulation studies (using the Desmond of Schrodinger software) and interaction analysis (using STRING database). The ß-CA protein found to be interacting with carbonic anhydrase protein family along with T27A3, alh13, mtp18, T22F3, gcy29 proteins. These results provide insights for the understanding of the functional and biological roles played by ß CA. Hence, this data is useful for the design of drugs for Ascariasis.

Distribution of various histopathological types of ovarian tumors: A study of 212 cases from a tertiary care center of Eastern Uttar Pradesh.

BACKGROUND: Ovarian tumors are one of the leading cancers in females with variable pathological types. This study describes the distribution, clinical and pathological details of various histopathological types of ovarian tumors in a tertiary care hospital in North India. MATERIALS AND METHODS: A retrospective data of 3 years were collected for ovarian tumors submitted to the pathology department of a tertiary care hospital. Data were classified according to the latest World Health Organization (WHO) Classification into epithelial tumors, germ cell tumors, sex cord-stromal tumors, and others. RESULTS: A total of 212 cases of ovarian tumors were studied, 186 were unilateral and 26 were bilateral. Resection specimen, part of specimen, and block review formed 80.2%, 15.1%, 4.7%, respectively. Epithelial tumors formed the majority in 71.7% of cases followed by germ cell tumors (22.2%), sex cord-stromal tumors (3.8%) and others (2.3%). Maximum number of cases in the respective groups occurred in the age groups 31-40, 21-30, 51-60, and 41-50 years, respectively. Overall, benign tumors were 63.7%, malignant tumors were 31.1%, and borderline were 5.2%. The most common histopathological type of benign and malignant tumor was benign serous cystadenoma (18.8%) and serous carcinoma (9.9%), respectively. CONCLUSION: In the present study, ovarian tumors were classified according to the WHO classification, epithelial and germ cell tumors were the major types of ovarian tumors. Benign epithelial tumor formed the majority with 46.2% cases. Serous cystadenoma and mature cystic teratoma were the predominant type of epithelial and germ cell tumors, respectively.

C-cell hyperplasia in sporadic and familial medullary thyroid carcinoma.

CONTEXT: C-cell hyperplasia (CCH) is characterized by increased mass of C-cells and has been identified as a precursor condition for medullary thyroid carcinoma (MTC). Varying proportion of MTCs is associated with CCH in different studies. This could be due to the lack of uniformity of the definitions and techniques used to identify CCH in these studies. AIMS: This study aims to study the occurrence, clinicopathological, and immunohistochemical features of CCH in MTC diagnosed during a 22-year period at a tertiary care center in North India and to review the available literature on CCH. MATERIALS AND METHODS: Eighty-seven consecutive cases of MTC were included in the study. Histological evaluation for the presence of CCH and neoplastic CCH was performed. Confirmation of CCH was done by immunohistochemistry for calcitonin and chromogranin. The presence of neoplastic CCH was correlated with clinical factors and prognostic factors. RESULTS: Of 87 cases of MTC included in the study, 71 (82%) patients were sporadic and 16 (18%) had familial MTC. Neoplastic CCH was seen in 12 (75%) familial and in 9 (13%) sporadic MTC. Patients with familial MTC were more frequently associated with neoplastic CCH than sporadic MTC (P < 0.001), were younger (P < 0.001), and had more often bilateral and multifocal tumors (P < 0.001). However, there was no significant difference in mean survival time and progression-free survival in patients with and without CCH. CONCLUSION: CCH, though more common in familial MTC, can also be seen in sporadic tumors. CCH is not associated with patient survival and disease progression.

Extranodal histiocytic sarcoma in a child with acute lymphoblastic leukemia: Cytomorphological features of a rare entity with brief review of literature.

Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic evidence of histiocytic differentiation. We describe a rare case of synchronous HS in a patient of B-cell acute lymphoblastic leukemia (ALL). A 16-year-old boy diagnosed as ALL also presented with a swelling over the right Achilles tendon. The cytological features of the swelling suggested a histiocytic lesion. Histological and immunohistochemical examination clinched the diagnosis of HS. The available 5-year follow-up showed no recurrence. It was a diagnostic dilemma on fine-needle aspiration. We discuss the cytological features of HS which can help in reaching a diagnosis and emphasize that it should be considered in the differential diagnosis for unexplained swellings in patients of hematological malignancies. Wide local excision of localized HS is associated with a long-term favorable outcome.

Clinico-hematological Profile of Hb E-ß Thalassemia-Prospective Analysis in a tertiary Care Centre.

INTRODUCTION: Hemoglobin E beta-thalassemia is one of the leading forms of severe thalassemia world wide. This disorder is more commonly found in South East Asia including north eastern states of India. Patients suffering from this disorder show marked clinical heterogeneity. MATERIALS AND METHODS: Referred cases of hemoglobin disorders from north India were evaluated prospectively. Details of clinical history and haematological findings including HPLC as well as mutation analysis were obtained. RESULTS: Twenty cases of E beta-thalassemia with widely variable clinical profile were included. The hematological parameters were also extremely variable with a wide range of hemoglobin (1.8-9.9 g/dl). Applying a severity scoring system all patients were classified the patients into mild (n=6), moderate (n=7) and severe (n=7) subclasses. We also correlated red cell Indies with HB E and HB F as well as age of onset of symptoms with HB E and HB F. IVS1-5(G-C) was found to be the most common thalassemia mutation associated with Hemoglobin E beta-thalassemia. CONCLUSION: Extremely variable clinical and haematological findings were observed in Hemoglobin E beta-thalassemia patients. These findings are comparable to other Indian studies. Appropriate knowledge of the clinical variability and unpredictable natural history can help better management of this group of patients.

Extraskeletal mesenchymal chondrosarcoma at unusual location involving spleen and kidney with review of literature.

Mesenchymal chondrosarcoma (MC) is a rare malignant neoplasm bearing characteristic dimorphic pattern histologically. We describe two rare cases of primary MC involving two different visceral organs (1) a 24-year-old man with solid renal mass and, (2) a 42-year-old man with cystic splenic mass. The histological and immunophenotypical features of both lesions were classical of MC. Although this lesion is uncommon in visceral organs, the possibility of this rare entity must be kept in differential diagnosis with compatible morphology.