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1.
QJM ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790119

RESUMO

BACKGROUND: Scrub typhus was once thought to be a disease of rural origin and was confined to specific pockets in South Asia. Early diagnosis and treatment is extremely important as it is associated with high mortality if left untreated. AIM: To delineate the clinical and molecular epidemiology of scrub typhus in patients presenting with acute febrile illness from various parts of India. METHOD: During the study period of five years (October, 2013 to October, 2018), a total of 1742 patients with acute febrile illness <15 days were enrolled after taking informed consent. Patients were diagnosed using IgM Enzyme linked immunosorbent assay (ELISA) based on the pre-determined region specific cut-offs. Patients with positive IgM ELISA were also subjected to IgM Immunofluorescence assay (IFA) and nested polymerase chain reaction assay (PCR). The demographic and relevant clinical details of the patients were documented and analyzed. RESULT: A total of 210 (12.1%) patients were diagnosed with scrub typhus. Of these, nested PCR was positive in only 85 patients. Sequencing and phylogenetic analysis showed that the predominant circulating genotypes were Gilliam and Karp. On multivariate analysis, acute respiratory distress syndrome, myocarditis, encephalitis/encephalopathy, jaundice and splenomegaly were significantly more common in those patients who were diagnosed with scrub typhus. A total of 14 patients diagnosed with scrub typhus succumbed to the illness. CONCLUSION: Patients with fever, headache, pulmonary manifestations, CNS manifestations, myocarditis, transaminitis or thrombocytopenia presenting in the monsoon and post-monsoon season should be evaluated for scrub typhus irrespective of the geographical location in India.

2.
BMJ Case Rep ; 12(11)2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31748366
4.
Opt Express ; 27(22): 31567-31586, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684389

RESUMO

In this article, we describe active steering of radiation patterns by complex nanoantenna structures - called steerable nanoantennas (SNs) - formed by combining multiple Yagi-Uda nanoantennas and thin films of a phase change material (VO2). The radiation patterns of these nanoantennas can be actively steered by tunably changing the phase of the VO2 thin films from the semiconductor phase to the metallic phase. Moreover, the nanoantennas enable steering of the radiation patterns 'in the plane' of the nanoantennas. We demonstrate that the radiation pattern's maximum achievable steering is 90° for a two-element steerable nanoantenna when the phase of the VO2 thin film is changed from the semiconductor phase to the metallic phase. Moreover, it was observed that the radiation pattern of the steerable nanoantennas being proposed in our paper can be designed to be much more directed than previously reported steerable nanoantennas. By employing a four element steerable nanoantenna, we also demonstrate a full 360° active steering of the radiation pattern. This steerable nanoantenna consists of four coplanar Yagi-Uda nanoantennas, with each Yagi-Uda nanoantenna being present inside a VO2 thin film but each individually addressable VO2 thin film being separated from the other VO2 films by an air gap. We demonstrate that the radiation pattern can be tunably steered in 12 different directions using this four element steerable nanoantenna depending on the states of the four VO2 thin films. The steerable nanoantennas can find applications in areas such as tunable on chip plasmonic interconnects, networks on chip, or for selective excitation of fluorophores on a sensor chip.

5.
QJM ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642501

RESUMO

Zika virus is an arthropod-borne flavivirus that presents with acute febrile illness associated with rash, arthralgia and conjunctivitis. After years of sporadic reports in Africa, the three major outbreaks of this disease occurred in Yap Islands (2007), French Polynesia (2013-2014) and South Americas (2015-2016). Although, serological surveys suggested the presence of ZIKV in India in 1950s, cross reactivity could not be ruled out. The first four proven cases of ZIKV from India were reported in 2017. This was followed by major outbreaks in the states of Rajasthan and Madhya Pradesh in 2018. Fortunately, the outbreaks in India were not associated with neurological complications. These outbreaks in India highlighted the spread of this disease beyond geographical barriers owing to the growing globalization, increased travel and ubiquitous presence of its vector, the Aedes mosquito. We discuss the epidemiology, clinical features, management of Zika virus in India in this review.

6.
QJM ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613366
7.
Chem Senses ; 44(9): 693-703, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31665762

RESUMO

Computational prediction of how strongly an olfactory receptor (OR) responds to various odors can help in bridging the widening gap between the large number of receptors that have been sequenced and the small number of experiments measuring their responses. Previous efforts in this area have predicted the responses of a receptor to some odors, using the known responses of the same receptor to other odors. Here, we present a method to predict the responses of a receptor without any known responses by using available data about the responses of other conspecific receptors and their sequences. We applied this method to ORs in insects Drosophila melanogaster (both adult and larva) and Anopheles gambiae and to mouse and human ORs. We found the predictions to be in significant agreement with the experimental measurements. The method also provides clues about the response-determining positions within the receptor sequences.

8.
Infez Med ; 27(3): 308-315, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545775

RESUMO

With significant advancement in the tools and strategies available for diagnosis and management, there is an expected change in the epidemiological profile of patients living with HIV/AIDS (Human immunodeficiency syndrome/Acquired immunedeficiency syndrome). We retrospectively analyzed the changing epidemiological pattern of HIV infection over a period of 13 years in the anti-retroviral (ART) center of a tertiary care hospital in India. The study included a total of 9419 patients (8811 adults and 608 children) who were registered at our ART center between 2005 and 2017. Among adult patients, 68.9% patients were males and the mean age of presentation was 35.6±9.9 years. Heterosexual route was the most common route of transmission (95.5%). A total of 97.4% of pediatric patients acquired HIV infection via vertical transmission from their mothers. Most of the adult patients (77.1%) were educated only to primary level. Despite the economic growth in the country over the years, the monthly income of these patients has not significantly changed. The median CD4 count at the time of eligibility for starting ART was 244/µl of blood. An increasing trend in the baseline CD4 count was noticed from 2005 to 2017. Also, improved outcomes with less loss to follow up were noticed in the latter years. However, an increasing trend was also noted in the time gap between registration at the ART center and initiation of ART. Improvement in the baseline CD4 count and better treatment outcomes are indicators of a well-functioning national program. However, continued programmatic interventions are needed to further tackle the menace of HIV/AIDS in India.

9.
J Assoc Physicians India ; 67(9): 85-86, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561697

RESUMO

Tuberculosis (TB) is an important cause of significant morbidity and mortality, particularly in patients living with human immunodeficiency virus (HIV ) infections. The co-infection of TB and HIV coinfection is further complicated by a relatively higher frequency of extra-pulmonary TB and upsurge of drug resistance. Musculoskeletal TB is a relatively less common form of extrapulmonary TB; involvement of carpometacarpal joint as an initial manifestation is even rarer. We herein present a retro positive patient who presented with low-grade fever, constitutional features and swelling of the base of the left thumb. On evaluation, he was found to have axillary and inguinal lymphadenopathy with lytic destruction of carpometacarpal joint as well as D10-D11 vertebrae. Fine needle aspiration (FNA) of synovial fluid was negative for tuberculosis but geneXpert from FNA of axillary node revealed Mycobacterium tuberculosis with rifampicin resistance. This case highlights the rarity of carpometacarpal joint involvement in TB as the initial manifestation and the importance of meticulous search of alternative sites for sampling in difficult situations such as osteoarticular TB. It also highlights the rising prevalence of drug-resistant TB and a definitive need for microbiological diagnosis wherever feasible.


Assuntos
Articulações Carpometacarpais , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Osteoarticular/diagnóstico , Infecções por HIV , Humanos , Masculino , Osteomielite
10.
Indian J Med Res ; 149(6): 790-794, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31496533

RESUMO

Scrub typhus is largely ignored in India particularly during outbreaks of viral fever. The disease course is often complicated leading to fatalities in the absence of treatment. However, if diagnosed early and a specific treatment is initiated, the cure rate is high. We report here five cases of scrub typhus to highlight the fact that high clinical suspicion for such a deadly disease is an absolute necessity.

12.
Nature ; 571(7765): 398-402, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292548

RESUMO

A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by the Paneth cell niche1,2. Here we show that the regenerative potential of human and mouse intestinal epithelium diminishes with age owing to defects in both stem cells and their niche. The functional decline was caused by a decrease in stemness-maintaining Wnt signalling due to production of Notum, an extracellular Wnt inhibitor, in aged Paneth cells. Mechanistically, high activity of mammalian target of rapamycin complex 1 (mTORC1) in aged Paneth cells inhibits activity of peroxisome proliferator activated receptor α (PPAR-α)3, and lowered PPAR-α activity increased Notum expression. Genetic targeting of Notum or Wnt supplementation restored function of aged intestinal organoids. Moreover, pharmacological inhibition of Notum in mice enhanced the regenerative capacity of aged stem cells and promoted recovery from chemotherapy-induced damage. Our results reveal a role of the stem cell niche in ageing and demonstrate that targeting of Notum can promote regeneration of aged tissues.


Assuntos
Envelhecimento , Senescência Celular , Esterases/metabolismo , Mucosa Intestinal/patologia , Celulas de Paneth/metabolismo , Regeneração , Envelhecimento/fisiologia , Animais , Senescência Celular/fisiologia , Esterases/antagonistas & inibidores , Esterases/biossíntese , Feminino , Humanos , Mucosa Intestinal/fisiologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , PPAR alfa/metabolismo , Celulas de Paneth/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Nicho de Células-Tronco , Células-Tronco/patologia , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt
13.
Int J Biochem Cell Biol ; 114: 105567, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295552

RESUMO

The biggest challenge in delivering anticancer agents is the ability to direct these molecules specifically to cancer cells. With this in mind, modern research is focussing on improving the precision of cancer drug delivery by incorporating a ligand that has the ability to specifically recognize cancer cells. Peptides are emerging as a new tool in drug and gene delivery. Peptide-drug conjugates, peptide-modified drug delivery systems, and peptide-coupled imaging agents have been shown to increase on-site delivery. This has allowed better tumor mass contouring in imaging and increased therapeutic efficacy of chemotherapies, reducing adverse effects. Benefits of peptide ligands include their small size, easy and affordable production, high specificity and remarkable flexibility regarding their sequence and conjugation possibilities. Bombesin (Bn) receptors have shown great promise for tumor targeting due to their increased expression in a variety of human cancers, including prostate, breast, small cell lung, and pancreatic cells. This review discusses the overexpression of Bn receptors in different cancers and various approaches to target these receptors for therapeutic and diagnostic interventions in human malignancies.

15.
Pan Afr Med J ; 32: 105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223395

RESUMO

Haemophagocytic lymphohistiocytosis (HLH) in Human Immunodeficiency Virus (HIV) infected individuals can either be due to the disease itself or due to associated infections/malignancies. The treatment for HLH requires immunosuppressive therapy but administering immunosuppressive therapy to an already immunosuppressed patient (HIV infection) is complex. We present two such cases of HLH in patients infected with HIV. In the first case, no alternate cause for HLH was found even after extensive investigations and it was attributed to the uncontrolled HIV replication. Patient was started on dexamethasone for the same but succumbed to hospital acquired pneumonia. The second patient was diagnosed with Hodgkin's lymphoma but he succumbed to his illness before initiating immunosuppressive therapy for HLH. We report these cases to highlight the dilemma and a need for further research in this direction.


Assuntos
Infecções por HIV/complicações , Imunossupressores/efeitos adversos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Adulto , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Infecções por HIV/imunologia , Humanos , Imunossupressores/administração & dosagem , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Pessoa de Meia-Idade
16.
Pan Afr Med J ; 32: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143348

RESUMO

Histoplasmosis is an endemic mycosis with global distribution, primarily reported in immunocompromised individuals. A 29-year old immunocompetent male presented with fever, hepatosplenomegaly and pancytopenia. His peripheral blood showed features suggestive of intravascular hemolysis and echocardiography showed features suggestive of pulmonary arterial hypertension. Bone marrow showed yeast with morphology suggestive of Histoplasma capsulatum. Further investigations revealed hyperferritinemia, hypofibrinogenemia and increased triglycerides. With a diagnosis of progressive disseminated histoplasmosis with secondary Haemophagocytic lymphohistiocytosis, he was successfully treated with amphotericin B followed by itraconazole. We report this case to highlight the atypical and rare manifestations of histoplasmosis.


Assuntos
Antifúngicos/administração & dosagem , Insuficiência Cardíaca/etiologia , Histoplasmose/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Anfotericina B/administração & dosagem , Febre/etiologia , Hemólise , Hepatomegalia/etiologia , Histoplasmose/complicações , Histoplasmose/tratamento farmacológico , Humanos , Imunocompetência , Itraconazol/administração & dosagem , Masculino , Pancitopenia/etiologia , Esplenomegalia/etiologia
17.
Inflamm Bowel Dis ; 25(11): 1854-1861, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31050734

RESUMO

BACKGROUND: Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn's disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. METHODS: We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014-June 2015 (Era 1) and July 2015-June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. RESULTS: A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease-related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. CONCLUSION: Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.

18.
Drug Discov Ther ; 13(2): 96-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080209

RESUMO

Oligoarticular arthritis (inflammation of upto 4 joints) has a wide range of infectious and non-infectious etiologies. The aim of our study was to identify the features which could help in the differentiation of infectious from non-infectious arthritis. The study was prospective and observational, and included 100 patients with oligoarticular inflammatory arthritis. The final diagnosis was made using standard diagnostic criteria and the patients were categorized into infectious and non-infectious groups. Among the 100 patients who were recruited, the following final diagnosis were made: peripheral spondyloarthritis (n = 37), axial spondyloarthritis (n = 11), tuberculosis (n = 19), brucellosis (n = 6), septic arthritis (n = 6), gouty arthritis (n = 5), early rheumatoid arthritis (n = 5), non-tubercular mycobacteria (n = 2), SLE (n = 2), post-chikungunya arthritis (n = 2), acute lymphocytic leukaemia (n = 1), pachydermoperiostosis (n = 1), sarcoidosis (n = 1) and juvenile idiopathoic arthritis (n = 1). The patients were categorized into two groups: infectious (33) and non-infectious (60). The presence of monoarthritis, clinically-significant weight loss, hepatomegaly, splenomegaly and erosive arthritis were significantly more common in the infectious group as compared to the non-infectious group.


Assuntos
Artrite Infecciosa/epidemiologia , Artrite/classificação , Doenças não Transmissíveis/epidemiologia , Adolescente , Adulto , Artrite/diagnóstico , Artrite Gotosa/diagnóstico , Artrite Gotosa/epidemiologia , Artrite Infecciosa/diagnóstico , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Brucelose/diagnóstico , Brucelose/epidemiologia , Feminino , Humanos , Índia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sarcoidose/epidemiologia , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Centros de Atenção Terciária , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adulto Jovem
19.
J Hosp Med ; 14: E1-E5, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897058
20.
Br J Haematol ; 185(5): 818, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30891729
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