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Nucleoid-associated proteins (NAPs) regulate multiple cellular processes such as gene expression, virulence, and dormancy throughout bacterial species. NAPs help in the survival and adaptation of Mycobacterium tuberculosis (Mtb) within the host. Fourteen NAPs have been identified in Escherichia coli; however, only seven NAPs are documented in Mtb. Given its complex lifestyle, it is reasonable to assume that Mtb would encode for more NAPs. Using bioinformatics tools and biochemical experiments, we have identified the heparin-binding hemagglutinin (HbhA) protein of Mtb as a novel sequence-independent DNA-binding protein which has previously been characterized as an adhesion molecule required for extrapulmonary dissemination. Deleting the carboxy-terminal domain of HbhA resulted in a complete loss of its DNA-binding activity. Atomic force microscopy showed HbhA-mediated architectural modulations in the DNA, which may play a regulatory role in transcription and genome organization. Our results showed that HbhA colocalizes with the nucleoid region of Mtb. Transcriptomics analyses of a hbhA KO strain revealed that it regulates the expression of â¼36% of total and â¼29% of essential genes. Deletion of hbhA resulted in the upregulation of â¼73% of all differentially expressed genes, belonging to multiple pathways suggesting it to be a global repressor. The results show that HbhA is a nonessential NAP regulating gene expression globally and acting as a plausible transcriptional repressor.
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Proteínas de Bactérias , Hemaglutininas , Mycobacterium tuberculosis , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , DNA/química , DNA/metabolismo , Hemaglutininas/genética , Hemaglutininas/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Deleção de Genes , Proteínas de Ligação a DNA/genética , Domínios Proteicos/genética , Microscopia de Força AtômicaRESUMO
BACKGROUND: Hepatitis B is a serious public health concern and health care professionals especially nurses are at higher risk of acquiring this infection. Basic knowledge, awareness and a positive attitude are required to prevent this disease. OBJECTIVE: The present pilot study was conducted to assess awareness and attitude regarding hepatitis B among staff nurses and nursing students of a teaching hospital in north India. MATERIAL AND METHODS: A total of 205 subjects who gave consent to participate were included in this descriptive study. A self-structured pre-tested close ended questionnaire comprising of two parts was used to collect information from the study subjects. First part collected information on demographic details of the study subject and second part assessed subjects' awareness and attitude on various aspects of hepatitis B infection including vaccination. Chi-square test and multiple linear regression analysis was used for statistical analysis. RESULTS: The mean age of the study subjects was 25.8±5.6 years. Awareness regarding HBV infection was present among 92.6% (190) of subjects. Long-term effects of hepatitis B were known to 58.4% (119) of subjects and 79.1% (162) of subjects reported taking universal precautions. Half of the subjects (105), were getting regularly tested for hepatitis B antigen.The odds of getting regularly tested for hepatitis B antigen were 3.26 times greater in female subjects and 3.45 times greater in subjects who were GNMs. CONCLUSION: Low awareness levels were reported regarding some important aspects of hepatitis B among study subjects though more than 90% were aware of it. There is an urgent need for education and training programs for nurses designed to increase their knowledge about HBV infection.
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Conhecimentos, Atitudes e Prática em Saúde , Hepatite B , Hospitais de Ensino , Estudantes de Enfermagem , Humanos , Feminino , Masculino , Adulto , Hepatite B/prevenção & controle , Hepatite B/psicologia , Índia , Projetos Piloto , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , Adulto Jovem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Inquéritos e Questionários , Atitude do Pessoal de SaúdeRESUMO
Addisonian pigmentation usually presents with nonspecific symptoms and signs, which are often ignored or misdiagnosed as a sign of other more common diseases. We present a case of 12-year-old child in whom diffuse Addisonian hyperpigmentation of skin was associated with underlying acute lymphoblastic leukemia (B-type), a rare paraneoplastic phenomenon in hematological malignancies.
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Hiperpigmentação , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Hiperpigmentação/etiologia , Pele , PigmentaçãoRESUMO
OBJECTIVES: Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol. METHODS: In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03-8â mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations. RESULTS: There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired ß-lactamase activity also could not explain the range in cefiderocol susceptibility. CONCLUSIONS: The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.
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Farmacorresistência Bacteriana Múltipla , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , CefiderocolRESUMO
Omicron, the new 'Variant of Concern' of SARS-CoV-2, is rapidly evolving into new sub-variants or sub-lineages (BA.1, BA.2 etc.). These sub-variants have higher transmissibility, decreased vaccine effectiveness and increased risk of reinfection. As a result, many nations across the globe are reporting surge in infections which is a matter of concern. Understanding Omicron and its sub-variants is vital for development of public health policy and preventing disease transmission. The present paper throws a spotlight on the newly detected sub-variants of Omicron as reported in ongoing researches which are available only in pre-print form and also the importance of a booster dose of the vaccine. Information regarding recent research on a new nasal vaccine formulation, which may be effective against the new variants, is also highlighted in the paper.
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COVID-19 , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Eficácia de VacinasRESUMO
The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the efficacy of such treatments has been observed in both preclinical studies and clinical trials, there are issues pertaining to the use of these drugs which require more extensive research with regards to the delivery and stability of siRNAs and ASOs. This would improve their use for long-term treatment regimens and alleviate the difficulties experienced by patients with ocular diseases. This review provides a detailed insight into the recent developments and clinical trials that have been conducted for several gene-silencing therapies, including ISTH0036, SYL040012, SYL1001, PF-04523655, Sirna-027, QR-110, QR-1123, QR-421a and IONIS-FB-LRX in glaucoma, dry eye disease, age-related macular degeneration, diabetic macular oedema and various inherited retinal diseases. Our aim is to explore the potential of these drugs whilst evaluating their associated advantages and disadvantages, and to discuss the future translation of RNA therapeutics in ophthalmology.
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Terapia Genética/métodos , Glaucoma/terapia , Degeneração Macular/terapia , Edema Macular/terapia , Oligonucleotídeos Antissenso/uso terapêutico , RNA Interferente Pequeno/uso terapêutico , Doenças Retinianas/terapia , Ensaios Clínicos como Assunto , Inativação Gênica , Humanos , Pesquisa Translacional BiomédicaRESUMO
The COVID-19 pandemic has challenged clinicians to recognize COVID-19 as one of the diagnostic explanation for common presentations, including fever, cough, and shortness of breath. Latent tuberculosis is responsible for 80% of active tuberculosis cases in the United States, and presentation can vary from asymptomatic to disseminated disease. This potential diagnosis should be thoroughly investigated in foreign-born patients in US hospitals, regardless of travel history and presenting symptoms. We report a patient diagnosed with postpartum disseminated tuberculosis with hematogenous spread to the fetus.
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DivIVA or Wag31, which is an essential pole organizing protein in mycobacteria, can self-assemble at the negatively curved side of the membrane at the growing pole to form a higher order structural scaffold for maintaining cellular morphology and localizing various target proteins for cell-wall biogenesis. The structural organization of polar scaffold formed by polymerization of coiled-coil rich Wag31, which is implicated in the anti-tubercular activities of amino-pyrimidine sulfonamides, remains to be determined. A single-site phosphorylation in Wag31 regulates peptidoglycan biosynthesis in mycobacteria. We report biophysical characterizations of filaments formed by mycobacterial Wag31 using circular dichroism, atomic force microscopy and small angle solution X-ray scattering. Atomic force microscopic images of the wild-type, a phospho-mimetic (T73E) and a phospho-ablative (T73A) form of Wag31 show mostly linear filament formation with occasional curving, kinking and apparent branching. Solution X-ray scattering data indicates that the phospho-mimetic forms of the Wag31 polymers are on average more compact than their phospho-ablative counterparts, which is likely due to the extent of bending/branching. Observed structural features in this first view of Wag31 filaments suggest a basis for higher order Wag31 scaffold formation at the pole.
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Proteínas de Bactérias/ultraestrutura , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mycobacterium tuberculosis/ultraestrutura , Peptidoglicano/ultraestrutura , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Peptídeos e Proteínas de Sinalização Intercelular/química , Microscopia de Força Atômica , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Peptidoglicano/química , Peptidoglicano/genética , Fosforilação , Transporte Proteico/genética , Ecrans Intensificadores para Raios XRESUMO
BACKGROUND: Mineral Pitch (MP) is a dark brown coloured humic matter originating from high altitude rocks. It is an Ayurvedic medicinal food, commonly used by the people of the Himalayan regions of Nepal and India for various body ailments. METHODS: The Huh-7 cells were treated with different concentrations of MP for 24 h, and both apoptosis and proliferation was determined by the TUNEL and MTT assays respectively. The formation of ROS and nitric oxide was analysed by DCFH-DA and Griess reagent respectively. The expression of miRNA-21 and miRNA-22 were checked by the real time PCR. Effect of miRNA-22 on proliferation and c-myc was studied by over-expressing miRNA-22 premiRs in Huh-7 cells. RESULTS: We found that MP enhanced anti-cancer effects by inducing apoptosis and inhibiting proliferation. MP induced both ROS and NO, upon neutralizing them, there was a partial recovery of apoptosis and proliferation. MP also induced miRNA-22 expression, while miRNA-21 expression was inhibited. Over-expression of miRNA-22 resulted in a significant inhibition of proliferation. miRNA-22 directly targeted c-myc gene, thereby inhibited proliferation. These results clearly show that MP induces its anti-cancer activity by more than one pathway. CONCLUSION: The data clearly indicate that MP induced apoptosis via the production of ROS, and inhibited proliferation by inducing miRNA-22 and inhibiting miRNA-21 in Huh-7 cells.
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Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Substâncias Húmicas , Neoplasias Hepáticas/tratamento farmacológico , Minerais/uso terapêutico , Resinas Vegetais/uso terapêutico , Antioxidantes/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Hepatócitos , Humanos , Medicina Tradicional , MicroRNAs/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Imatinib and nilotinib are inhibitors of tyrosine kinases (TKIs) generated from the bcr-abl fusion protein, c-Kit, and platelet-derived growth factor receptors. Cutaneous adverse effects (AEs) of TKI are the most frequent non-hematological sequelae. In our case, the common molecular target raises the possibility that cross-intolerance, in which similar AEs occur with both agents, can arise. We hereby report a rare case report on cross-intolerance of cutaneous AEs of imatinib and nilotinib in chronic myeloid leukemia.
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PURPOSE: This study aimed to evaluate the efficacy and safety of Keraring implantation followed by simultaneous topography-guided photorefractive keratectomy (TGPRK) and corneal cross-linking (CXL) in the management of keratoconus. METHODS: This is a single-center, private practice, retrospective review. Patients with keratoconus who were intolerant to contact lens wear underwent implantation of the Keraring, followed by TGPRK with CXL from 2 to 36 months after implantation. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction (cylinder and spherical equivalent), keratometry (steep, maximum, and central), and central corneal thickness (CCT). Patients were followed up for 3 to 60 months postoperatively. RESULTS: Fifty-seven eyes from 45 patients were included. The mean time between Keraring and TGPRK/CXL was 6.0 ± 6.0 months. Patients were followed up for a mean of 28.6 ± 20.1 months after Keraring insertion. At 12-month follow-up, there was a statistically significant improvement in mean UDVA (0.94 ± 0.49-0.35 ± 0.23, P < 0.01), CDVA (0.39 ± 0.26-0.17 ± 0.15, P < 0.01), cylinder (-4.97 ± 2.68 to -1.74 ± 1.25, P < 0.01), steep keratometry (51.25 ± 3.37-45.03 ± 2.27, P < 0.01), central keratometry (52.59 ± 4.98-46.99 ± 3.53, P < 0.01), and maximum keratometry (58.78 ± 4.22-50.76 ± 3.42, P < 0.01). These results were sustained at 48-month follow-up. CCT decreased at 12 months after TGPRK (461.84 ± 27.46-418.94 ± 45.62, P < 0.01) and remained stable at 60 months. Postoperatively, 2 eyes (3.51%) had corneal haze, resulting in decrease in CDVA; 1 was treated successfully with repeat PRK; and 1 patient (1.75%) had wound melt due to partial Keraring extrusion, which settled with repositioning. CONCLUSIONS: Keraring implantation followed by simultaneous TGPRK and CXL appears to be effective in the long term in improving UDVA, CDVA, cylinder, CCT, and keratometry in patients with keratoconus who are intolerant to contact lenses.
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Lentes de Contato , Ceratocone , Ceratectomia Fotorrefrativa , Humanos , Ceratectomia Fotorrefrativa/métodos , Ceratocone/tratamento farmacológico , Ceratocone/cirurgia , Crosslinking Corneano , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Substância Própria/cirurgia , Topografia da Córnea , Reagentes de Ligações Cruzadas/uso terapêuticoRESUMO
OBJECTIVE: To compare long-term effectiveness of Standard (UV intensity: 3 mW/cm2, duration: 30 min) vs Accelerated (UV intensity: 9 mW/cm2, duration: 10 min) corneal cross-linking (CXL) for stabilising keratoconus. METHODS: Data for this observational study were captured through a web-based registry system from the routine clinical practice (15 sites across Australia, New Zealand and Italy). The outcomes were compared using mixed-effects regression models. A total of 100 eyes (75 patients) who had standard CXL and 76 eyes (66 patients) who had accelerated CXL, with a follow-up visit at five-year post-CXL were included. RESULTS: Both CXL protocols were effective and safe in stabilising keratoconus and improving outcomes. The adjusted mean changes (95% CI) in outcomes were better in standard CXL than in accelerated CXL [visual acuity gain, 10.2 (7.9-12.5) vs 4.9 (1.6-8.2) logMAR letters; pinhole visual acuity 5.7 (3.5-7.8) vs 0.2 (-2.2 to 2.5) logMAR letters; Kmax -1.8 (-4.3 to 0.6) vs 1.2 (-1.5 to 3.9)D; K2 -0.9 (-2.2 to 0.3) vs 0.1 (-1.3 to 1.6)D; MCT -3.0 (-13.7 to 7.7) vs -11.8 (-23.9 to 0.4) µm (p values for visual acuity, pinhole visual acuity, Kmax: <0.05; for K2 and MCT: >0.05)]. The frequency of adverse events at the 5-year follow-up visit was low in both groups [standard, 5 (5%; haze 3; scarring 1, epithelial defect 1) and accelerated 3 (3.9%; haze 2, scarring 1)]. CONCLUSIONS: Both standard and accelerated CXL were safe and effective procedures for stabilising keratoconus in the long term. The standard CXL resulted in greater improvements in visual acuity and keratometry.
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Ceratocone , Fotoquimioterapia , Humanos , Ceratocone/tratamento farmacológico , Crosslinking Corneano , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Riboflavina/uso terapêutico , Raios Ultravioleta , Cicatriz , Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Sistema de Registros , Topografia da Córnea/métodos , SeguimentosRESUMO
Introduction: Primary hyperparathyroidism due to parathyroid adenoma commonly causes raised serum calcium and focal giant cell lytic lesions in bones known as Brown's tumors. It is more common in females in the post-menopausal age group. Case Report: We report a case of a 29-year-old female patient with Brown's tumor maxilla in a clinical setting of normocalcemic primary hyperparathyroidism. The patient presented to us with facial and palatal swelling for which FNAC was done. Cytology revealed hemosiderin-laden macrophages suspicious for Brown's tumor. On further imaging studies such as CT Neck, Tc99 Sestamibi scan, and other biochemical tests like parathyroid hormone assay and serum calcium level, the diagnosis of a hyperfunctioning parathyroid gland with normal calcium level was made. Parathyroidectomy was performed and parathyroid adenoma came out to be the primary pathology. On post-operative follow up there was regression of the swelling on the face and palate relieving the patient symptomatically. Conclusion: The diagnostic suspicion of primary hyperparathyroidism should be kept in mind whenever a young female presents with suspected Brown's tumor, even with normal serum calcium levels, for appropriate management. Ours was a highly uncommon case that was a diagnostic challenge and had a successful treatment outcome. Very few such cases have been reported in the literature to date to the best of our knowledge.
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Background and Purpose The ongoing coronavirus disease 2019 (COVID-19) pandemic is a multisystemic disease and involvement of the nervous system is well established. The neurological and neuroimaging features of the disease have been extensively evaluated. Our study aimed to elucidate the neuroradiological findings in COVID-19 infected patients admitted to our institute during the first and second waves of the pandemic in India. Methods This was a single-center retrospective study of all COVID-19 positive patients who underwent neuroimaging between March 2020 and May 2021. The presenting neurological complaints, the imaging findings in computed tomography (CT) imaging, and/or magnetic resonance imaging (MRI) were recorded. They recorded the findings in the subheadings of ischemic stroke, hemorrhagic stroke, parainfectious demyelination, acute encephalitis syndrome, and changes of global hypoxic changes. Patients with age-related, chronic, and incidental findings were excluded. Results The study comprised of 180 COVID-19 positive patients who underwent neuroimaging. CT scan was performed for 169 patients, MRI for 28, and a combination of both CT and MRI was performed for 17 patients. Seventy percent of patients were males, and median age was 61.5 years (interquartile range: 48.25-70.75). Out of the 180 patients, 66 patients had nonspecific findings that could not be attributed to COVID-19 infection. In the remaining 114 patients, 77 (42.7%) had ischemic findings, while 22 (12.2%) had hemorrhagic stroke. Hypoxic ischemic changes were noted in five patients. The rest of the patients had a spectrum of changes including, cerebellitis (3), tumefactive demyelination (1), COVID-19-associated encephalitis (1), hemorrhagic acute demyelinating encephalomyelitis (1), transverse myelitis (1), cytotoxic lesions of corpus callosum (1), Guillain-Barre syndrome (1), and COVID-19-associated microhemorrhages (1). Conclusion Neurological manifestations of COVID-19 infection are not uncommon, and our understanding of this topic is expanding. A complex interplay of neurotropism and direct central nervous system invasion, immune activation and cytokine storm, vasculitis, and parainfectious processes are implicated in the pathophysiology. While the most common imaging finding was ischemic stroke, followed by hemorrhagic stroke, a diverse range of parainfectious findings was also noted in our study.
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BACKGROUND: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors. METHODS: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both. RESULTS: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery. CONCLUSION: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis.
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COVID-19 , Transplante de Coração , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Transplante de Coração/efeitos adversos , Doadores de TecidosRESUMO
BACKGROUND: A prospective observational study in a university hospital setting to study the immunohistochemical (IHC) characteristics of non-neoplastic human lacrimal sac epithelium. METHODS: Twenty paraffin-embedded specimens of human lacrimal sac were studied using monospecific monoclonal antibodies to 34 beta E12, cell adhesion molecule (CAM 5.2), epithelial membrane antigen (EMA), cytokeratins (CK) 7 and 20, estrogen receptor and progesterone receptor. The distribution and histologic location of IHC staining were examined qualitatively, and the IHC stains scored as positive (+) or negative (-). RESULTS: The haematoxylin-eosin stains were reviewed for tissue morphology. All 20 specimens were positive for 34 beta E12, CAM 5.2, EMA and CK 7 and negative for CK 20, estrogen receptor and progesterone receptor. CONCLUSION: To our knowledge, this is the first study to characterize the IHC properties of human lacrimal sac epithelium. This epithelium appears to possess consistent IHC properties as it stains for 34 beta E12, CAM 5.2, EMA and CK 7 and this information would be potentially useful in differentiating tumours arising in the region of the lacrimal sac.
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Células Epiteliais/citologia , Aparelho Lacrimal/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Proteínas de Transporte/metabolismo , Epitélio , Feminino , Humanos , Técnicas Imunoenzimáticas , Queratinas/metabolismo , Aparelho Lacrimal/metabolismo , Masculino , Pessoa de Meia-Idade , Mucina-1/metabolismo , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
BACKGROUND/AIMS: Immunohistochemical characterisation of orbital cavernous haemangiomas (CHs) with respect to proliferative capacity, hormone receptor status and vascular differentiation. METHODS: Eleven cases of orbital CHs were reviewed. Immunohistochemical stains for Mib-1, proliferating cell nuclear antigen (PCNA), Bcl-2, estrogen and progesterone receptors (ER & PR), CD31, D2-40, and VEGF were investigated in 11 specimens. RESULTS: Immunohistochemical staining revealed positivity for PCNA in ten of the 11 cases (91%). Bcl-2 was positive in 8 cases (73%). VEGF and PR were each weakly positive in 3 cases. All cases were negative for Mib-1, ER and D2-40. The staining was localized around the endothelium. CONCLUSION: This is the first study to characterise in detail the immunohistochemical features of orbital CHs. The proliferative markers PCNA and Mib-1 show discordant expression in these lesions and the expression of PCNA and Bcl-2 in the absence of Mib-1 is indicative of low proliferative potential. Small subsets of these tumors express PR and VEGF, which may partly explain the proliferative capacity of some orbital CHs.
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Biomarcadores Tumorais/metabolismo , Hemangioma Cavernoso/metabolismo , Neoplasias Orbitárias/metabolismo , Anticorpos Monoclonais Murinos/metabolismo , Diferenciação Celular , Proliferação de Células , Humanos , Imuno-Histoquímica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Immunosuppression changes both susceptibility to and presentation of infection. Infection with one pathogen can also alter host response to a different, unrelated pathogen. These interactions have been seen across multiple infection domains where bacteria, viruses or fungi act synergistically with a deleterious impact on the host. This phenomenon has been well described with bacterial and fungal infections complicating influenza and is of particular interest in the context of the COVID-19 pandemic. Modulation of the immune system is a crucial part of successful solid organ and hematopoietic stem cell transplantation. Herein, we present three cases of polymicrobial infection in transplant recipients. These case examples highlight complex host-pathogen interactions and the resultant clinical syndromes.
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COVID-19 , Coinfecção , Transplante de Células-Tronco Hematopoéticas , Humanos , Pandemias , Hospedeiro Imunocomprometido , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Infections due to extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed blaTEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 µg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 µg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.
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Escherichia coli , Klebsiella pneumoniae , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/farmacologia , Ceftibuteno , Ceftizoxima/análogos & derivados , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , CefpodoximaRESUMO
Seasonal and occupational exposure of the human body to extreme cold temperatures can result in cell death in the exposed area due to the formation of ice crystals. This leads to superficial or deep burn injury and compromised functionality. Currently available therapeutics can be ineffective in extreme cases, and thus, it is necessary to develop prophylactic strategies. In this study, we have devised a combination of known synthetic cryopreservative agents (termed SynAFP) and evaluated their potential antifreeze applications on skin. The prophylactic activity of SynAFP in vitro is indicated by improved cellular revival and cell viability, retention of the cytoskeleton, and normal cell cycle progression even after cold stress. A comprehensive whole-cell proteomic approach revealed that in the presence of SynAFP, cold-induced downregulation of proteins involved in cell-cell adhesion and upregulation of those related to mitochondrial stress were ameliorated. Pre-application of SynAFP in mice facing a frostbite challenge prevents their skin from incurring significant injury as confirmed through macroscopic and histological examination. Moreover, multiple applications of SynAFP on mouse skin at room temperature did not compromise skin integrity. SynAFP was also formulated in anAloe vera-based cream (referred to as fSynAFP), which offered similar protection under cold stress conditions. Thus, SynAFP can be considered as a potential candidate for formulating a topical intervention for protection from cold-induced injuries to skin.