SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021.

Background: COVID-19 emerged as a global pandemic in 2020, spreading rapidly to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via serosurveillance, making it a valuable tool for planning control measures. Our serosurvey study aimed to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. Methods: This cross-sectional survey, conducted in January 2021 and including males and females aged 10 years and above, used multi-stage random sampling. 9363 samples were collected from 30 wards distributed over six zones of Hyderabad, and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. Results: Overall seropositivity was 54.2%, ranging from 50% to 60% in most wards. Highest exposure appeared to be among those aged 30-39 and 50-59 years, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for COVID-19 testing. Conclusion: Over half the city's population was infected within a year of onset of the pandemic. However, ∼ 46% of people remained susceptible, contributing to subsequent waves of infection.

Expression of the E2A-PBX1 fusion transcripts in t(1;19)(q23;p13) and der(19)t(1;19) at diagnosis and in remission of acute lymphoblastic leukemia with different B lineage immunophenotypes.

The chromosomal translocation t(1;19)(q23;p13) and its variant form der(19)t(1;19) found in 3-5% of acute lymphoblastic leukemia (ALL) results in the expression of the E2A-PBX1 fusion transcript. Although strongly associated with a pre-B immunophenotype, we report the occurrence of t(1;19) in bone marrow or peripheral blood in nine patients with ALL with the following immunophenotypes: pre-B ALL (four), c-ALL (two), c-ALL clg not tested (one), null-ALL (one) and mature B-ALL (one). The E2A-PBX1 fusion transcript investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) was seen in all patients at diagnosis and/or on follow-up samples. Six patients are alive in first clinical remission. Of these patients, three were PCR+ve from between 2 and 38 months from diagnosis, and three were PCR-ve when examined at 5, 26 and 51 months from diagnosis. Two patients are in second remission. One was PCR+ve at 18 months, suffered a CNS relapse at 21 months but was PCR-ve 1 month later. The other was PCR+ve in remission at 2 and 11 months from diagnosis and in testicular relapse at 31 months, but was PCR-ve 5 months later. The remaining patient died 2 months from diagnosis and was not investigated in remission. The prognostic significance of these findings remains to be investigated.

E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia.

Three cases of acute lymphoblastic leukemia (ALL) with the rare t(17;19)(q22;p13) translocation were investigated for E2A/HLF fusion genes using reverse transcription coupled with polymerase chain reaction (RT-PCR). The patients had C-ALL, F/17 years (case 1) or pre-B ALL, M/11 years (case 2) and M/13 years (case 3). Case 1 had an event-free survival (EFS) of 42 months. Case 2 was ultimately refractory to treatment. Case 3 presented following EFS of 16 months in morphological remission (1% blasts), but with immunological and cytogenetic evidence of active disease, then relapsed, remitted and relapsed. Type II E2A/HLF fusion cDNA was found at diagnosis (cases 1, 2), at presentation (case 3) and in all samples tested, whether with active disease or in complete remission (CR). Case 3 showed, in addition, type I fusion E2A/HLF cDNA at presentation, through induction therapy when there was evidence of active disease, but not in CR. Cases 1 and 3 had bone marrow transplantation while in CR but with residual disease detectable by RT-PCR. All patients have died of ALL. Two cases (2 and 3) had hypercalcemia with bone lesions. No case had any evidence of disseminated intravascular coagulation. This is the first demonstration of the value of RT-PCR for the detection of minimal residual disease in t(17;19) ALL.

Relapse of acute promyelocytic leukemia follows serial negative RT-PCR assays: a cautionary tale.

Six patients with acute promyelocytic leukaemia (APL) and t(15;17) were investigated by cytogenetics and by reverse transcriptase polymerase chain reaction (RT-PCR) for the fusion transcript PML-RARA. The clone was detected in remission following all-trans retinoic acid and chemotherapy by cytogenetics and/or by RT-PCR up to 2 months from diagnosis. Thereafter the PML-RARA transcript was not seen in 20/21 first remission samples in five cases studied. Remission was maintained in two patients, one following bone marrow transplantation (BMT). Despite serial negative RT-PCR results, PML-RARA reemerged at or prior to relapse following BMT in the remaining three cases. Frequent molecular monitoring and caution in the interpretation of negative RT-PCR results are indicated in APL.

Relationship between acetylcholinesterase and monoamine oxidase in brain regions of Oreochromis mossambicus exposed to phosalone.

The level of acetylcholinesterase (AChE) in brain regions of O. mossambicus at different intervals showed the extent of phosalone toxicity. Significant inhibition of AChE at the end of 96 hr in the brain regions was observed. In contrast to AChE inhibition, the monoamine oxidase (MAO) activity showed significant increase in the regions of cerebral hemispheres, dien/mesencephalon, cerebellum and medulla oblongata. The increase of MAO activity in the brain regions under phosalone toxicity is considered to be one of the mechanisms to maintain the amines level in O. mossambicus.

Interrelationship between amines level in brain regions of fish, Oreochromis mossambicus during organophosphorus stress.

Amines such as dopamine, norepinephrine and epinephrine were analysed in the brain regions of O.mossambicus exposed to quinalphos, phenthoate and their combination for 96 hr. The three types of treatments significantly (P < 0.05) altered the amines level at various intervals in the brain regions.

Neuronavigation with the universal probe to access intracranial targets.

INTRODUCTION: The universal probe is a tool devised to allow navigation-directed biopsies and drainage procedures to be performed in a simple manner using a single hardware and software. AIM: To assess the efficacy and safety of the universal probe. RESULTS: We used the universal probe in a total of 17 patients for 10 biopsies and 8 drainage procedures. We were able to achieve our set objectives in all 18 procedures. We did not encounter any complications using this device. CONCLUSION: The universal probe enabled a variety of navigation-based procedures to be carried out using only a single software and hardware.

Three-dimensional anatomical accuracy of cranial models created by rapid prototyping techniques validated using a neuronavigation station.

In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7®.

Intervention for suicide attempters: A randomized controlled study.

AIM: To determine whether brief intervention and contact (BIC) is effective in reducing subsequent suicidal behavior among suicide attempters. MATERIALS AND METHODS: Suicide attempters (n=680) admitted in a general hospital in Chennai were randomly allocated to treatment as usual and BIC whose components include brief intervention at the time of discharge and contact for 18 months. RESULTS: Completed suicide was significantly lower in the BIC group, OR 35.4 (CI 18.4 - 78.2) as also attempted suicide, OR 17.3 (CI 10.8 - 29.7). CONCLUSIONS: This low-cost intervention which can be readily implemented may be an important suicide prevention strategy in healthcare settings in India.

Characterization of the superinduction of the c-myc proto-oncogene in fibroblasts by benzamide derivatives.

In mouse fibroblasts stimulated from quiescence into proliferation by serum the induction of expression of the c-myc proto-oncogene is strongly stimulated by 3-methoxybenzamide. Similar superinduction effects are seen with related compounds such as 3-aminobenzamide and the acid analogues, 3-anisic acid and 3-aminobenzoic acid. Whereas the benzamide derivatives are inhibitors of poly(ADP-ribose) polymerase the acid analogues are not, suggesting that inhibition of this enzyme is not the basis for superinduction of the c-myc gene. Analysis of the kinetics of induction of c-myc mRNA indicates that the RNA accumulates more rapidly as well as to a higher level in the presence of serum plus 3-methoxybenzamide than with serum alone. However the stimulation is transient in both cases. Addition of actinomycin D at 30 min or 1 h after serum stimulation shows the c-myc mRNA to be stable at these times, in the presence or absence of 3-methoxybenzamide. Thus the effect of the latter on c-myc mRNA accumulation is likely to be exerted at the level of transcription or RNA processing rather than turnover of the mRNA.

RANTES binding and down-regulation by a novel human herpesvirus-6 beta chemokine receptor.

The human herpesvirus 6 (HHV-6) U51 gene defines a new family of betaherpesvirus-specific genes encoding multiple transmembrane glycoproteins with similarity to G protein-coupled receptors, in particular, human chemokine receptors. These are distinct from the HHV-6 U12 and HCMV US28 family. In vitro transcription and translation as well as transient cellular expression of U51 showed properties of a multiple transmembrane protein with a 30-kDa monomer as well as high m.w. aggregates or oligomers. Transient cellularly expressed U51 also appeared to form dimeric intermediates. Despite having only limited sequence similarity to chemokine receptors, U51 stably expressed in cell lines showed specific binding of the CC chemokine RANTES and competitive binding with other beta chemokines, such as eotaxin; monocyte chemoattractant protein 1, 3, and 4; as well as the HHV-8 chemokine vMIPII. In epithelial cells already secreting RANTES, U51 expression resulted in specific transcriptional down-regulation. This correlated with reduced secretion of RANTES protein into the culture supernatants. Regulation of RANTES levels may alter selective recruitment of circulating inflammatory cells that the virus can infect and thus could mediate the systemic spread of the virus from initial sites of infection in epithelia. Alternatively, chemokine regulation could modulate a protective inflammatory response to aid the spread of virus by immune evasion. Such mimicry, by viral proteins, of host receptors leading to down-regulation of chemokine expression is a novel immunomodulatory mechanism.

Detection of BCR-ABL and E2A-PBX1 fusion genes by RT-PCR in acute lymphoblastic leukaemia with failed or normal cytogenetics.

To evaluate the use of molecular analysis as a complement to karyotypic analysis in the detection of specific chromosomal abnormalities, the occurrence of t(1;19)(q23;p13) and t(9;22)(q34;q11) was investigated by RT-PCR in 43 diagnostic acute lymphoblastic leukaemia cases in whom cytogenetic investigations had failed (32 cases) or showed only a normal karyotype (> or = 20 normal metaphases, 11 cases). One child (aged 14 years) and five adults (aged 18-60 years) were BCR-ABL positive on first round for M-BCR-ABL (one case) or m-BCR-ABL (one case), or on nested PCR for m-BCR-ABL (three cases). Co-expression of M-BCR-ABL (first-round PCR) and m-BCR-ABL (nested PCR was seen in one case. One m-BCR-ABL-positive case also expressed the E2A-PBX1 fusion transcript. Patients positive for the transcript(s) were older, had higher white blood cell counts and a significantly poorer event-free survival (P < 0.001) than those negative for the transcript.

Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3.

Demonstration of either the translocation t(15;17)(q22;q21) or the fusion of PML and RARalpha genes is regarded as diagnostic for acute myeloid leukaemia (AML) of FAB type M3, but has occasionally been seen in other FAB types. We present two such cases. Case 1 presented with FAB type M6 and a complex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent marrow dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. Fluorescence in situ hybridization (FISH) of metaphase chromosomes at diagnosis showed insertion of material from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RARalpha. Case 2 presented as AML M4 and relapsed as M3. Cytogenetic analysis at diagnosis and in relapse showed 46,XY,t(15;17)(q22;q11),del(16)(q22). FISH analysis showed this to be a three-way translocation involving chromosomes 15, 16 and 17 again with juxtaposition of PML and RARalpha. Reverse transcription-polymerase chain reaction (RT-PCR) revealed PML/RARalpha fusion at diagnosis, in remission and in first relapse. These examples strengthen the case for RT-PCR screening of all AML patients for these fusion genes.

Two types of genomic rearrangements create alternative E2A-HLF fusion proteins in t(17;19)-ALL.

The t(17;19)(q21-q22;p13.3) in acute lymphoblastic leukemia results in creation of an E2A-HLF fusion protein with structural and functional properties of a chimeric transcription factor. Two types of genomic rearrangements underlie fusion of E2A with HLF. In type I rearrangements, an insertion that codes for a portion of the chimera not found in either wild type protein occurs between E2A exon 13- and HLF exon 4-encoded sequences. This insertion is derived from a cryptic exon created at the junction between chromosomes 17 and 19, and includes intronic portions of both E2A and HLF with intervening nontemplated N nucleotides. Type II rearrangements arise from more 5' breakpoints in E2A and result in fusion cDNAs with E2A exon 12 spliced directly to HLF exon 4. Analysis of the genomic structure of HLF shows that these different modes of protein fusion result from selective constraints to maintain the proper HLF reading frame, because a direct E2A exon 13 to HLF exon 4 splice would lead to translation of a truncated E2A protein lacking any contribution from HLF. These features underscore the requirement for DNA binding and/or dimerization conferred by the bZIP portion of the E2A-HLF chimera in t(17;19)-ALL.

A case of mature B-cell ALL with coexistence of t(1;19) and t(14;18) and expression of the E2A/PBX1 fusion gene.

The translocation t(1;19)(q23;p13) is found in 3-5% of all acute lymphoblastic leukaemias (ALL) and results in the expression of an E2A/PBX1 hybrid gene transcript. This translocation is very closely associated with a pre-B phenotype. t(14;18) is associated with follicular B-cell lymphoma and is characterized by over-expression of the bcl-2 oncogene. We describe a case of ALL in an adult with a mature B-cell immunophenotype and a single abnormal cell line with a complex karyotype showing both t(1;19) and t(14;18). Two reports of this phenomenon have been published previously and molecular analysis, where performed, showed the E2A gene was not rearranged, suggesting the t(1;19) was a molecular variant of the established translocation. In contrast, molecular analysis of our case demonstrated expression of the E2A/PBX1 fusion transcript typically associated with t(1;19) in pre-B ALL but showed it to be present at an extremely low level, despite the abnormal karyotype being found in the majority of metaphase cells. Analysis of bcl-2 expression showed a significant up-regulation. A down-regulation of the E2A/PBX1 hybrid gene as a consequence of the enhanced expression of bcl-2 may be a possible mechanism for this finding.