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1.
Exp Neurol ; 329: 113319, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305418

RESUMO

Heterozygous mutations in the X-linked gene CASK are associated with intellectual disability, microcephaly, pontocerebellar hypoplasia, optic nerve hypoplasia and partially penetrant seizures in girls. The Cask+/- heterozygous knockout female mouse phenocopies the human disorder and exhibits postnatal microencephaly, cerebellar hypoplasia and optic nerve hypoplasia. It is not known if Cask+/- mice also display seizures, nor is known the molecular mechanism by which CASK haploinsufficiency produces the numerous documented phenotypes. 24-h video electroencephalography demonstrates that despite sporadic seizure activity, the overall electrographic patterns remain unaltered in Cask+/- mice. Additionally, seizure threshold to the commonly used kindling agent, pentylenetetrazol, remains unaltered in Cask+/- mice, indicating that even in mice the seizure phenotype is only partially penetrant and may have an indirect mechanism. RNA sequencing experiments on Cask+/- mouse brain uncovers a very limited number of changes, with most differences arising in the transcripts of extracellular matrix proteins and the transcripts of a group of nuclear proteins. In contrast to limited changes at the transcript level, quantitative whole-brain proteomics using iTRAQ quantitative mass-spectrometry reveals major changes in synaptic, metabolic/mitochondrial, cytoskeletal, and protein metabolic pathways. Unbiased protein-protein interaction mapping using affinity chromatography demonstrates that CASK may form complexes with proteins belonging to the same functional groups in which altered protein levels are observed. We discuss the mechanism of the observed changes in the context of known molecular function/s of CASK. Overall, our data indicate that the phenotypic spectrum of female Cask+/- mice includes sporadic seizures and thus closely parallels that of CASK haploinsufficient girls; the Cask+/- mouse is thus a face-validated model for CASK-related pathologies. We therefore surmise that CASK haploinsufficiency is likely to affect brain structure and function due to dysregulation of several cellular pathways including synaptic signaling and cellular metabolism.

2.
J Dent Res ; 99(4): 362-373, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32122215

RESUMO

Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank's classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care.

3.
4.
Trop Anim Health Prod ; 52(1): 357-363, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31376061

RESUMO

The study evaluated the reliability of polymorphonuclear (PMN) cell count in endometrial cytology by cytobrush technique as a diagnostic for subclinical endometritis (SCE) at the time of estrus and its relationship with bacterial presence and fertility in buffaloes. Healthy pluriparous buffaloes (n = 115) were subjected to endometrial sampling by cytobrush technique (for cytology and bacterial isolation) and ultrasonography of genitalia prior to insemination at the time of spontaneous estrus. Buffaloes were inseminated at the same estrus and were confirmed for pregnancy by ultrasonography at day 40 post-insemination. Growth of aerobic bacteria was recorded in 26.1% (30/115) of estrual buffaloes. Bacteria of eight distinct genera (Staphylococcus spp., Bacillus spp., Proteus spp., Escherichia coli, Klebsiella spp., Streptococcus spp., Pseudomonas spp. and T. pyogenes) were isolated. Presence of bacterial infection was considered as the standard, against which PMN threshold for SCE was calculated by receiver operator curve (ROC). The PMN count of ≥ 5% with good sensitivity (66.7, 95% CI 50.9-81.4) and specificity (87.0%, 95% CI 78.0-94.6) with an overall high diagnostic accuracy (81.7%) for predicting SCE was obtained. Based on calculated PMN threshold, buffaloes were divided into subclinical endometritic (SCE; ≥ 5% PMNs) and control (< 5% PMNs) groups. Thirty-one buffaloes (27.0%, 31/115) had ≥ 5% PMNs in the endometrial cytology at estrus. Ultrasonographic evaluation showed that size of largest follicle, endometrial thickness, and uterine horn diameter did not differ significantly (P > 0.05) between the two groups. Significantly, lower conception rate (22.58 vs 36.90%, P < 0.05) for first artificial inseminations (AIs) and significantly higher number of AIs per pregnancy (2.81 ± 0.27 vs 1.75 ± 0.15, P < 0.05) were recorded in SCE compared to control group. The results indicated that cytobrush based endometrial cytology with 5% PMN cut-off value has a good accuracy for predicting subclinical endometritis at estrus in buffaloes.

6.
J Hosp Infect ; 103(3): 280-283, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31170422

RESUMO

The aim of the study was to assess antimicrobial prescribing patterns, and variation in practice, in India. A point prevalence survey (PPS) was conducted in October to December 2017 in 16 tertiary care hospitals across India. The survey included all inpatients receiving an antimicrobial on the day of PPS and collected data were analysed using a web-based application of the University of Antwerp. In all, 1750 patients were surveyed, of whom 1005 were receiving a total of 1578 antimicrobials. Among the antimicrobials prescribed, 26.87% were for community-acquired infections; 19.20% for hospital-acquired infections; 17.24% for medical prophylaxis; 28.70% for surgical prophylaxis; and 7.99% for other or undetermined reasons. Antibiotic prescribing quality indicators, such as reason in notes and post-prescription review score, were low. This PPS showed widespread antibiotic usage, underlining the need for antibiotic stewardship to promote evidence-based practice.


Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Humanos , Índia , Inquéritos e Questionários , Centros de Atenção Terciária
7.
J Postgrad Med ; 65(2): 81-86, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30860079

RESUMO

Background: Thyroid Natural Orifice Transluminal Endoscopic Surgery (NOTES) or transoral endoscopic thyroidectomy using vestibular approach is a recent advance embraced by the surgical community because of its potential for a scar-free thyroidectomy. In this article, we present our initial experience with this technique. Materials and Methods: We used a three-port technique through the oral vestibule, one 10 mm port for the laparoscope and two additional 5 mm ports for the endoscopic instruments required. The carbon dioxide insufflation pressure was set at 12 mm of Hg. Anterior cervical subplatysmal space was created from the oral vestibule down to the sternal notch, and the thyroidectomy was done using conventional laparoscopic instruments and a harmonic scalpel. Results: From May 2016 to December 2017, we have performed ten such procedures in the Department of General Surgery in our hospital, which is a tertiary referral center. Six patients had solitary thyroid nodules, for which a hemi-thyroidectomy was done. Four patients had multi-nodular goiter and total thyroidectomy or near-total thyroidectomy was done. The preoperative fine-needle aspiration cytology (FNAC) was suggestive of Bethesda class 2 lesions in all the patients with multinodular goiter and in five of the six patients with solitary nodular goiter. Only one patient with solitary nodular goiter had a Bethesda class 3 lesion on FNAC. The final histopathological report of the specimen was benign, either colloid goiter, or degenerative nodule in all cases of multinodular goiter and in four cases of solitary thyroid nodule. In one Bethesda class 2 solitary nodule, the histopathological report was suggestive of follicular carcinoma; in the Bethesda class 3 solitary nodule, the histopathological report was suggestive of follicular variant of papillary carcinoma. No complication such as temporary or permanent vocal cord paralysis, hypoparathyroidism, subcutaneous emphysema, pneumomediastinum, tracheal injury, esophageal injury, mental nerve palsy, or surgical site infection was found postoperatively. However, two patients developed small hematomas in the midline. Conclusion: Transoral endoscopic thyroidectomy is a safe, feasible, and minimally invasive technique with excellent cosmetic results.

8.
Acute Med ; 18(4): 210-215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31912051

RESUMO

BACKGROUND: Inter-hospital communication frequently requires mediation via a switchboard. Identifying and eliminating switchboard inefficiencies may improve patient care. METHODS: All 175 acute hospital switchboards in England were contacted six times. Call contents and duration were recorded. No clinician calls or bleeps were connected. RESULTS: The mean delay before contacting a switchboard operative was 55±46 seconds. 115 hospitals (66%) used automated switchboards; 34 of these (30%) had infection control messages. Robot operators introduced an additional 40 second delay versus humans (mean 70.3±28 versus 29.8±23 seconds, p<0.0001). Multivariate analysis identified robot operators (HR 5.1, p<0.0001) and infection control messages (HR 2.9, p=0.003) as predictors of delays over 60 seconds. CONCLUSIONS: There are significant avoidable delays in contacting switchboard operatives across England. Quality improvement is underway.


Assuntos
Comunicação , Hospitais , Melhoria de Qualidade , Medicina Estatal , Inglaterra , Humanos
9.
J Biosci ; 43(4): 707-715, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30207316

RESUMO

Antibiotic resistance in bacteria is a major health concern. Antimicrobial peptides (AMPs) are a class of peptides that are efficient in killing most microbes yet development of resistance to AMPs is rare. However, complex secondary and tertiary structures and difficulties in isolating AMPs have limited their use as antibiotics. It has been demonstrated earlier that small peptides derived from human ß defensin-3 (HBD-3) also show antibacterial activity. Here, we perform a detailed characterization of the antibacterial activity of one such derivative: CHRG01. While HBD-3 has 45 amino acids with three disulphide bonds and a ß-sheet folded structure, CHRG01 has only 14 amino acids with the cysteine residues replaced by serine. The antibacterial nature of CHRG01 was studied using scanning electron microscopy (SEM), confocal microscopy, circular dichroism (CD) and small-angle X-ray scattering (SAXS). CD data show that CHRG01 is random coiled in solution. SEM and confocal studies show that the mode of action of CHRG01 is pore forming. SAXS studies show that CHRG01 induces a negative Gaussian curvature, the type of curvature needed for pore formation. The above results show that CHRG01, a small peptide without any complex structure, is capable of killing bacteria by permeabilizing their outer membranes.


Assuntos
Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Bactérias/efeitos dos fármacos , beta-Defensinas/química , Sequência de Aminoácidos/genética , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/patogenicidade , Dicroísmo Circular , Humanos , Testes de Sensibilidade Microbiana , Conformação Proteica em Folha beta , Difração de Raios X , beta-Defensinas/genética , beta-Defensinas/farmacologia
10.
Bioresour Technol ; 256: 110-117, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29433045

RESUMO

In the present work, xylan from arecanut husk was extracted using 2 stage alkaline pretreatment process. In first step, biomass was incubated in alkali at different temperatures (25 °C, 50 °C and 65 °C), alkali concentrations (5%, 10%, 15% and 20% w/v), and incubation periods (8 h, 16 h and 24 h) and evaluated for xylan recovery. It was observed that 40-52% of available xylan could be recovered using 10% alkali when incubated for 8-24 h at 65 °C. Subsequently, the alkali pretreatment operating conditions which provided good xylan recovery were processed further using hydrothermal treatment to extract more xylan. For maximum xylan recovery (>90%), best operating conditions were identified when biomass was treated under hydrothermal treatment (1, 1.5 and 2 h) with varying incubation periods (8, 16, 24 h) and alkali concentrations (5%, 10%) using full factorial design. Incubating arecanut husk with 10% w/v NaOH, at 65 °C for a period of 8 h, followed by hydrothermal treatment at 121 °C for 1 h helped recover >94% xylan. In the next step, enzymatic hydrolysis process was optimized to recover maximum XOS (Optimized condition: 50 °C, pH 4 and 10 U enzyme dose). The hydrolysate comprised of xylobiose: 25.0 ±â€¯1.2 g/100 g xylan (∼71% of XOS), xylotriose: 9.2 ±â€¯0.65 g/100 g xylan (26.2% of XOS) and xylotetrose: 0.9 ±â€¯0.04 g/100 g xylan (2% of XOS). The developed process enables to reduce alkali consumption for high recovery of xylan from biomass with relatively higher lignin content for its valorisation into a potential prebiotic oligosaccharide.


Assuntos
Glucuronatos , Oligossacarídeos , Xilanos , Álcalis , Biomassa , Endo-1,4-beta-Xilanases , Hidrólise , Lignina
11.
Aging Clin Exp Res ; 30(3): 271-275, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29305795

RESUMO

With an ageing population, surgical procedures in older patients are becoming increasingly more common. This can pose clinical and ethical dilemmas, during which clinicians need to make complex decisions. In this paper we discuss the importance of assessing mental capacity to assess if the older patient can make his or her own decisions relating to surgery. We also discuss the importance of understanding ethical principles, in order that clinicians can better guide patient's decision-making. In addition, we look at ageism, frailty, and co-morbidities, and their influence on clinician's decisions regarding surgery in older patients. Further to this, we look at the influence of evidence-based medicine on treatment options, and the under representation of older people in clinical trials and the importance of this. Finally, we consider the importance of considered decisions regarding resuscitation, when considering surgical intervention in older patients. We conclude that patient-centred individualised care, considering patients expectations, wishes, and priorities is vital, whilst aiming to improve or maintain quality of life, and minimise risks when able.


Assuntos
Preferência do Paciente , Assistência Centrada no Paciente , Procedimentos Cirúrgicos Operatórios , Tomada de Decisões , Ética Médica , Humanos , Qualidade de Vida
12.
J Laryngol Otol ; 132(12): 1093-1096, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30674362

RESUMO

BACKGROUND: Work describing patient and family outcomes after tracheostomy has indicated that patients do not feel prepared at the time of discharge. OBJECTIVES: To assess healthcare professional-patient interactions in tracheostomy care and the current provision of care. METHOD: A global electronic survey was disseminated via e-mail. RESULTS: The majority of respondents were nursing or speech and language staff, from over 10 countries. Only 23 per cent of respondents' institutions routinely offered patients the ability to meet people with a tracheostomy pre-operatively. Only 31 per cent consistently provided or co-ordinated full nursing and equipment requirements on discharge. Only half of the institutions participated in tracheostomy quality improvement initiatives; less than one-third of these involved patients. CONCLUSION: The provision of tracheostomy care in hospital and at discharge can be improved. The current practice of clinician-led audit is becoming less viable; future initiatives should focus upon patient-centred outcomes to ensure excellence in healthcare delivery.


Assuntos
Participação do Paciente/estatística & dados numéricos , Padrões de Prática Médica/normas , Qualidade da Assistência à Saúde/normas , Traqueostomia/normas , Adulto , Idoso , Estudos Transversais , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/normas , Projetos Piloto , Padrões de Prática Médica/estatística & dados numéricos , Relações Profissional-Paciente , Melhoria de Qualidade/normas
13.
Oncogene ; 37(4): 522-533, 2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-28991227

RESUMO

Despite advances in biology and therapeutic modalities, existence of highly tumorigenic glioma stem-like cells (GSCs) makes glioblastomas (GBMs) invincible. N6-methyl adenosine (m6A), one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. Here, we report the crucial role of METTL3-mediated m6A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation. RNA immunoprecipitation studies identified SOX2 as a bonafide m6A target of METTL3 and the m6A modification of SOX2 mRNA by METTL3 enhanced its stability. The exogenous overexpression of 3'UTR-less SOX2 significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs. METTL3 binding and m6A modification in vivo required intact three METTL3/m6A sites present in the SOX2-3'UTR. Further, we found that the recruitment of Human antigen R (HuR) to m6A-modified RNA is essential for SOX2 mRNA stabilization by METTL3. In addition, we found a preferential binding by HuR to the m6A-modified transcripts globally. METTL3 silenced GSCs showed enhanced sensitivity to γ-irradiation and reduced DNA repair as evidenced from the accumulation of γ-H2AX. Exogenous overexpression of 3'UTR-less SOX2 in METTL3 silenced GSCs showed efficient DNA repair and also resulted in the significant rescue of neurosphere formation from METTL3 silencing induced radiosensitivity. Silencing METTL3 inhibited RasV12 mediated transformation of mouse immortalized astrocytes. GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. METTL3 transcript levels predicted poor survival in GBMs which are enriched for GSC-specific signature. Thus our study reports the importance of m6A modification in GSCs and uncovers METTL3 as a potential molecular target in GBM therapy.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , Metiltransferases/metabolismo , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição SOXB1/genética , Regiões 3' não Traduzidas/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Encéfalo/citologia , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Carcinogênese/genética , Desdiferenciação Celular/genética , Desdiferenciação Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/genética , Reparo do DNA/efeitos da radiação , Proteína Semelhante a ELAV 1/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Glioblastoma/radioterapia , Glioblastoma/cirurgia , Humanos , Metiltransferases/genética , Camundongos , Camundongos Nus , Mutagênese Sítio-Dirigida , Células-Tronco Neoplásicas/efeitos da radiação , RNA Mensageiro/metabolismo , Tolerância a Radiação/genética , Fatores de Transcrição SOXB1/metabolismo , Esferoides Celulares/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Vet Comp Oncol ; 16(1): E99-E108, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28871635

RESUMO

Oral squamous cell carcinoma (OSCC) is an aggressive and treatment-resistant malignancy in both feline and human patients. Recent work has demonstrated aberrant expression of fatty acid synthase (FASN) and an increased capacity for lipogenesis in human OSCC and other cancers. In human OSCC, inhibition of FASN decreased cell viability and growth in vitro, and diminished tumour growth and metastasis in murine preclinical models. This study aimed to characterize FASN as a therapeutic target in feline OSCC. Immunohistochemistry revealed high FASN expression in primary feline OSCC tumours, and FASN expression was detected in OSCC cell lines (3 feline and 3 human) by immunoblotting and quantitative real-time-polymerase chain reaction (qRT-PCR). Orlistat, a FASN inhibitor, substantially reduced cell viability in both feline and human OSCC lines, although feline cell lines consistently displayed higher sensitivity to the drug. FASN mRNA expression among cell lines mirrored sensitivity to orlistat, with feline cell lines expressing higher levels of FASN. Consistent with this observation, diminished sensitivity to orlistat treatment and decreased FASN mRNA expression were observed in feline OSCC cells following incubation under hypoxic conditions. Treatment with orlistat did not potentiate sensitivity to carboplatin in the cell lines investigated; instead, combinations of the 2 drugs resulted in additive to antagonistic effects. Our results suggest that FASN inhibition is a viable therapeutic target for feline OSCC. Furthermore, cats may serve as a spontaneous large animal model for human oral cancer, although differences in the regulation of lipogenesis between these 2 species require further investigation.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/enzimologia , Ácido Graxo Sintases/metabolismo , Neoplasias Bucais/veterinária , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/enzimologia , Doenças do Gato/tratamento farmacológico , Gatos , Linhagem Celular Tumoral , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/efeitos dos fármacos , Humanos , Immunoblotting/veterinária , Lactonas/farmacologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/enzimologia , Orlistate , Reação em Cadeia da Polimerase em Tempo Real/veterinária
15.
J Food Sci Technol ; 54(13): 4416-4426, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29184248

RESUMO

An experiment was conducted with twelve major Indian banana cultivars to investigate the molecular relationship between the differential accumulation of ß-carotene in peel and pulp of the banana fruit and carotenoid biosynthetic pathway genes. The high performance liquid chromatography showed that all banana cultivars accumulated two-three fold more ß-carotene in non-edible portion of the banana fruit. However, Nendran, a famous orange fleshed cultivar of South India, had high ß-carotene content (1362 µg/100 g) in edible pulp. The gene encoding Musa accuminata phytoene synthase (MaPsy) was successfully amplified using a pair of degenerate primers designed from Oncidium orchid. The deduced amino acid sequences shared a high level of identity to phytoene synthase gene from other plants. Gene expression analysis confirmed the presence of two isoforms (MaPsy1 and MaPsy2) of MaPsy gene in banana fruits. Presence of two isoforms of MaPsy gene in peel and one in pulp confirmed the differential accumulation of ß-carotene in banana fruits. However, Nendran accumulated more ß-carotene in edible pulp due to presence of both the isoforms of MaPsy gene. Thus, carotenoid accumulation is a tissue specific process strongly dependent on differential expression pattern of two isoforms of MaPsy gene in banana.

16.
Ann Oncol ; 28(12): 3015-3021, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29045506

RESUMO

Background: On the basis of historical data, patients with cancer of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than 1 year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next-generation sequencing in the evaluation and treatment of patients with CUP. Patients and methods: Under Institutional Review Board approval, we identified all CUP patients evaluated at our institution over a recent 2-year period. We documented demographic information, clinical outcomes, pathologic evaluations, next-generation sequencing of available tumor tissue, use of targeted therapies, and clinical trial enrollment. Results: We identified 333 patients with a diagnosis of CUP evaluated at our institution from 1 January 2014 through 30 June 2016. Of these patients, 150 had targeted next-generation sequencing carried out on available tissue. Median overall survival in this cohort was 13 months. Forty-five of 150 (30%) patients had potentially targetable genomic alterations identified by tumor molecular profiling, and 15 of 150 (10%) received targeted therapies. Dominant mutation signatures were identified in 21 of 150 (14%), largely implicating exogenous mutagen exposures such as ultraviolet radiation and tobacco. Conclusions: Patients with CUP represent a heterogeneous population, harboring a variety of potentially targetable alterations. Next-generation sequencing may provide an opportunity for CUP patients to benefit from novel personalized therapies.


Assuntos
Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Sequenciamento Completo do Exoma
17.
Ultramicroscopy ; 183: 104-108, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28396080

RESUMO

The antiferromagnetic to ferromagnetic phase transition in FeRh can be induced globally by either heating the material above its phase transition temperature or applying a combination of external stimuli (such as mechanical strain, electric/magnetic fields) on the material preheated close to its transition temperature. On the other hand, to locally induce this phase transition is more desirable for applications and requires a confined source of energy such as a focused laser beam. Here we combine laser excitation with X-ray magnetic imaging to determine the effect of laser heating on the local and transient magnetization of FeRh using time-resolved photoelectron emission microscopy. Excitation by an ultrashort laser pulse generates a local ferromagnetic state within 0.6ns which recovers its initial antiferromagnetic state after a further 2ns. The form of the domains during the growth and diminution of ferromagnetic ordering suggests an intrinsic speed limit for magnetic and structural changes.

18.
Eye (Lond) ; 31(4): 519-528, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28338667

RESUMO

PurposeThe purpose of the study was to investigate the outcomes of primary photodynamic therapy (PDT) for small pigmented posterior pole choroidal melanoma.Patients and methodsProspective interventional consecutive case series of 15 patients with small pigmented posterior pole choroidal melanoma, who were treated with three sessions of PDT and followed-up thereafter. Risk factors for failure were assessed and outcome measures at presentation were compared to those at last follow-up visit.ResultsTumor control was achieved in 12 (80%) patients in a median follow-up time of 15 months (mean 14, range 8-18). Three patients failed treatment, diagnosed in a median time of 5 months (mean 4, range 3-6), after first PDT. In all failed cases, lesions were 100% pigmented; de novo melanoma rather than transformed nevi and showed a radial growth pattern rather than increased thickness. All failed cases were subsequently successfully treated with radiotherapy. In this cohort, subretinal fluid (SRF) was significantly reduced (P<0.001), vision did not deteriorate (P=0.11) and even improved in patients with subfoveal SRF at presentation (P=0.018), tumor height significantly decreased (P=0.037) and no complications were recorded.ConclusionPrimary PDT was found to be a safe and efficient treatment modality for small pigmented posterior pole choroidal melanoma, achieving short-term tumor control in 80% of patients. PDT offers patients the opportunity to preserve vision by avoiding the retinopathy associated with conventional radiation treatments for choroidal melanoma. However, the long-term local control of these tumors remains uncertain.


Assuntos
Neoplasias da Coroide/tratamento farmacológico , Melanoma/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coroide/patologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Reino Unido , Verteporfina , Acuidade Visual
19.
Bone Joint Res ; 6(1): 66-72, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28108483

RESUMO

OBJECTIVES: The aim of this study was to systematically review the literature on measurement of muscle strength in patients with femoroacetabular impingement (FAI) and other pathologies and to suggest guidelines to standardise protocols for future research in the field. METHODS: The Cochrane and PubMed libraries were searched for any publications using the terms 'hip', 'muscle', 'strength', and 'measurement' in the 'Title, Abstract, Keywords' field. A further search was performed using the terms 'femoroacetabular' or 'impingement'. The search was limited to recent literature only. RESULTS: A total of 29 articles were reviewed to obtain information on a number of variables. These comprised the type of device used for measurement, rater standardisation, the type of movements tested, body positioning and comparative studies of muscle strength in FAI versus normal controls. The studies found that hip muscle strength is lower in patients with FAI; this is also true for the asymptomatic hip in patients with FAI. CONCLUSIONS: Current literature on this subject is limited and examines multiple variables. Our recommendations for achieving reproducible results include stabilising the patient, measuring isometric movements and maximising standardisation by using a single tester and familiarising the participants with the protocol. Further work must be done to demonstrate the reliability of any new testing method.Cite this article: E. Mayne, A. Memarzadeh, P. Raut, A. Arora, V. Khanduja. Measuring hip muscle strength in patients with femoroacetabular impingement and other hip pathologies: A systematic review. Bone Joint Res 2017;6:66-72. DOI: 10.1302/2046-3758.61.BJR-2016-0081.

20.
Indian J Otolaryngol Head Neck Surg ; 68(2): 163-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27340630

RESUMO

A late detection of hearing impairment in children can affect speech and language development. Otitis media with effusion (OME) associated with risk factors like recurrent upper respiratory tract infections (URTI) is considered the most common cause of silent hearing impairment among children. So this study was carried out to screen such at risk children for hearing impairment. The study was conducted on 1000 children in the age group of 2-12 years who presented to the OPD of ENT and Pediatrics Department, Govt Medical College with the complaint of recurrent URTI. The children were screened by history taking, general physical examination and local ENT examination. This was followed by impedance audiometry and pure tone audiometry (PTA, wherever indicated). Children with discharging ears and perforated tympanic membrane (TM) were excluded from the study. The most common presenting complaint was nasal discharge (67.9 %), followed by mouth breathing (66.3 %) and snoring (65 %). Only 16.2 % cases actually complained of some hearing impairment on exploratory history indicating the silent nature of OME. On examination 52.65 % cases had a normal looking TM whereas 41.2 % had a dull retracted TM. Results of impedance audiometry showed Type A graph in 56.75 %, Type B in 33.4 % indicating OME and Type C in 9.85 % indicating Eustachian tube dysfunction. PTA showed a mild conductive hearing loss in 26.7 % cases. OME is quite prevalent in high risk children and incidence of OME resulting in silent hearing impairment is quite high especially in young children having recurrent URTI. Impedance audiometry has been proved to be an objective screening tool for the same with a diagnostic accuracy of 87 % and thus under preventive audiology, it has a definite role in young children having recurrent URTI.

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