scholarly journals P2X7 receptor/NLRP3 inflammasome complex and a-synuclein/parkin balance in neo-diagnosed, treatment-naïve Parkinson disease: a prospective study

2020 ◽  
Author(s):  
Anna Solini ◽  
Chiara Rossi ◽  
Eleonora Santini ◽  
Martina Giuntini ◽  
Francesco Raggi ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Nlrp3 Inflammasome ◽  
Transcriptional Control ◽  
De Novo ◽  
Mechanistic Explanation ◽  
Intracellular Signalling ◽  
Newly Diagnosed ◽  
Treatment Naïve ◽  
One Year ◽  
A Prospective Study

Abstract Background Neuro, and likely systemic inflammation, with abnormal α-synuclein deposition, participate in the development of Parkinson’s disease (PD). The P2 × 7 receptor/NLRP3 inflammasome complex is upregulated in the brain of PD patients. Aim of this study was to explore whether the systemic activation of such complex might participate in the pathogenesis of PD. Methods Systemic expression and functional activity of the inflammasome were measured in 25 newly diagnosed PD patients and 25 controls at baseline and after twelve months of pharmacologic treatment, exploring the involved intracellular signalling and its epigenetic regulation. A putative mechanistic explanation of the results was validated in a murine model of neuroinflammation. Results De-novo PD patients were characterized by a systemic hyper-expression of the P2 × 7R/NLRP3 inflammasome platform, likely modulating circulating and lymphomonocyte α-synuclein, whose deposits represent the main pathogenetic factor of PD. A reduced JNK phosphorylation might be the involved intracellular signalling. miR-7 and miR-30, implied in the pathogenesis of PD and in the post-transcriptional control of α-synuclein and NLRP3 expression, were also increased in PD. After one year of usual anti-Parkinson treatments, such inflammatory platform was significantly reduced. In the substantia nigra of P2 × 7R KO mice, a neuroinflammatory stimulus induced a strong expression of parkin, a protective protein, suggesting that P2 × 7R activation might participate in the inflammatory damage occurring in specific brain areas also by inhibiting parkin expression. Conclusion Newly-diagnosed PD subjects display a systemic hyper-expression of the P2 × 7R/NLRP3 inflammasome platform that seems to modulate circulating and lymphomonocyte α-synuclein; a reduced JNK phosphorylation might be the intracellular signalling mediating this effect, undergoing an epigenetic regulation by miR-7 and miR-30. Trial registration ClinicalTrials.gov (NCT03918616).

scholarly journals Variability of core microbiota in newly diagnosed treatment-naïve paediatric Inflammatory Bowel Disease patients

2018 ◽  
Author(s):  
T.G.J. de Meij ◽  
E.F.J. de Groot ◽  
C.F.W. Peeters ◽  
N.K.H de Boer ◽  
C.M.F. Kneepkens ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
De Novo ◽  
Bacterial Species ◽  
Microbiota Composition ◽  
Newly Diagnosed ◽  
Faecal Microbiota ◽  
Healthy State ◽  
Treatment Naïve ◽  
Inflammatory Bowel

AbstractBACKGROUND & AIMSIntestinal microbiota is considered to play a crucial role in the aetiology of inflammatory bowel disease (IBD). We aimed to describe faecal microbiota composition and dynamics in a large cohort of children with de novo (naïve) IBD, in comparison to healthy paediatric controls (HC).METHODSIn this prospective study, performed at two tertiary centres, faecal samples from newly diagnosed, treatment-naïve paediatric IBD patients were collected prior to bowel cleansing for colonoscopy (t0) and 1, 3 and 6 weeks and 3 months after initiation of therapy. The microbial profiles of Crohn’s disease (CD) and Ulcerative colitis (UC) patients were compared with HC and linked to therapeutic response. Microbiota composition was analysed by IS-pro technology.RESULTSMicrobial profiles of 104 new IBD-patients (63 CD, 41 UC, median age 14.0 years) were compared to 61 HC (median 7.8 years). IBD was mainly characterised by decreased abundance of Alistipes finegoldi and Alistipes putredinis, which characterize a healthy state microbial core. The classifier including these core species as predictors achieved an AUC of the ROC curve of .87. Core bacteria tended to regain abundance during treatment, but did not reach healthy levels.CONCLUSIONFaecal microbiota profiles of children with de novo CD and UC can be discriminated from HC with high accuracy, mainly driven by a decreased abundance of species shaping the microbial core in the healthy state. Paediatric IBD can therefore be characterized by decreased abundance of certain bacterial species reflecting the healthy state rather than by the introduction of pathogens.

Evaluation of Breast Lumps by Ultrasound and Correlation with Histological Findings

2020 ◽  
Vol 23 (1) ◽  
pp. 10-12
Author(s):  
Nelema Jahan ◽  
Md. Mamunur Rahman ◽  
Mohammad Shahidul Alam ◽  
Md Saiful Islam
Keyword(s):  
Histopathological Examination ◽  
Breast Diseases ◽  
Histopathological Study ◽  
Common Symptom ◽  
Breast Lump ◽  
Histopathological Findings ◽  
Malignant Breast ◽  
Breast Lumps ◽  
One Year ◽  
A Prospective Study

Background: A breast lump is the most common symptom associated with both benign and malignant breast diseases. Therefore, a distinction of benign from malignant lump is of importance for proper management. Though a definitive diagnosis is possible with imaging for all the lesions, histopathological study is proven essential for confirming the diagnosis. Objective: The objective of this study was to evaluate the role of USG and histopathological findings of different breast lump in diagnosis and their comparison. Methods: A prospective study was conducted over a period of one year from January 2017 to December 2017. A total of 116 patients were included in this study. All breast lumps underwent surgery and the ultrasound findings of these lumps were compared with the histopathological findings. Data were collected from these patients by a preformed questionnaire and finally the data were analyzed. Results: Out of 116 patients only 21 cases were reported as malignant in ultrasound report but histopathology revealed 31 malignant patients. On histopathological examination 10 benign cases turned out to be malignant. Conclusion: The present study was undertaken to evaluate in diagnosing breast mass lesions individually by ultrasound and compared with histopathology for definitive management of a patient. Journal of Surgical Sciences (2019) Vol. 23 (1) : 10-12

Sustained normoglycemia in newly diagnosed type I diabetic subjects. Short-term effects and one-year follow-up

Diabetes ◽  
1984 ◽  
Vol 33 (10) ◽  
pp. 995-1001 ◽  
Author(s):  
K. Perlman ◽  
R. M. Ehrlich ◽  
R. M. Filler ◽  
A. M. Albisser
Keyword(s):  
Type I ◽  
Newly Diagnosed ◽  
Short Term ◽  
One Year ◽  
Short Term Effects

scholarly journals Zika RNA and Flavivirus-Like Antigens in the Sperm Cells of Symptomatic and Asymptomatic Subjects

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 152
Author(s):  
Hernan Vanegas ◽  
Fredman González ◽  
Yaoska Reyes ◽  
Edwing Centeno ◽  
Jayrintzina Palacios ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Time Frame ◽  
Sperm Cells ◽  
Human Semen ◽  
Zikv Infection ◽  
Virus Shedding ◽  
One Year ◽  
Asymptomatic Subjects ◽  
A Prospective Study ◽  
Male Subjects

Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in León to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (≥18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 × 106/mL vs. 63.5 × 106/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.

scholarly journals One-year outcomes of fixed-dosing Aflibercept therapy for pre treated and naive polypoidal choroidal vasculopathy patient

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hun Gu Choo ◽  
Jin Hae Lee ◽  
Hyun Sub Oh ◽  
Soon Hyun Kim ◽  
Yong Sung You ◽  
...  
Keyword(s):  
Polypoidal Choroidal Vasculopathy ◽  
Vision Loss ◽  
Case Series ◽  
Age Related Macular Degeneration ◽  
Research Information ◽  
Age Related ◽  
Case Series Study ◽  
Treatment Naïve ◽  
One Year ◽  
Choroidal Vasculopathy

Abstract Background Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV. Methods This was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first 3 months (the loading phase), and thereafter, once every 2 months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months. Results After 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (p< 0.001). Additionally, ten patients (40%) showed complete polyp regression. The treatment-naïve patients showed a statistically significant improvement in BCVA from 66.58 letters at baseline to 76.36 letters at 12 months, and a significant decrease in CSMT, from 462 to 243 um. In the pre-treated group, there was no change in BCVA (64.46 letters), and the decrease in CSMT from 356.08 to 303.69 um was not statistically significant. Conclusions The fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients. Trial registration Clinical Research Information Service (CRiS), Republic of Korea. Identifer: KCT0005798, Registered: Jan 20, 2021. Retrospectively registered, URL: https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=18546

Customised gold weight eyelid implantation in paralytic lagophthalmos

2008 ◽  
Vol 122 (10) ◽  
pp. 1088-1091 ◽  
Author(s):  
N Jayashankar ◽  
K P Morwani ◽  
M J Shaan ◽  
S R Bhatia ◽  
K T Patil
Keyword(s):  
Visual Acuity ◽  
Prospective Study ◽  
Study Design ◽  
Study Group ◽  
Upper Eyelid ◽  
Eyelid Closure ◽  
Gold Weight ◽  
One Year ◽  
A Prospective Study

AbstractGold eyelid implantation is widely considered the procedure of choice to reanimate the upper eyelid in paralytic lagophthalmos. Commercially supplied implants are not readily available in all places and are sometimes cumbersome to import.Objective:We aimed to devise a method whereby every surgeon performing gold eyelid implantation could have easy and quick access to the implant. Furthermore, we aimed to develop a means of creating an implant of the exact weight required for complete eyelid closure.Study design and setting:A prospective study was performed from 1997 to 2005 in a tertiary research hospital, involving 50 subjects requiring gold upper eyelid implantation and using the technique in question.Results:Only patients with a minimum follow up of one year were included in the study group. Symptoms improved in 96 per cent of subjects, who were able to dispense with eyedrops and eye ointments. Visual acuity improved in 92 per cent of patients. There were two extrusions amongst the early cases.Conclusion and significance:Customised gold eyelid implantation offers an alternative in regions where commercial implants are not easily obtained.

scholarly journals Pattern of Ear Diseases among Paediatric ENT Patient: An Experience from Tertiary Care Centre, Pokhara, Nepal

2012 ◽  
Vol 32 (2) ◽  
pp. 142-145 ◽  
Author(s):  
B Sigdel ◽  
R Nepali
Keyword(s):  
Tertiary Care ◽  
Age Group ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Suppurative Otitis Media ◽  
Ear Diseases ◽  
Paediatric Age ◽  
One Year ◽  
A Prospective Study ◽  
Nose And Throat

Introduction: Ear diseases are common in children mainly due to altered anatomy of Eustachian tube which is straighter in children as compared to that in adults. However, the cause of hearing loss in children is more varied, including the etiologies. This study was done to find out the pattern of ear diseases in paediatric age group attending ear, nose and throat OPD in a tertiary care centre in Pokhara, Nepal. Materials and Methods: This is a prospective study done in paediatric patients attending ENT OPD over a period of one year from January 2010 to January 2011. The diagnoses were made on the basis of history and clinical examination. Results were expressed in numbers and percentages. Results: Out of 1632 Pediatric ENT patients, 944 had ear diseases, 59.2% were males and 40.8% females. Wax (33.4%) was the commonest diagnosis followed by Chronic suppurative otitis media (24.3%) and Acute ottitis media (13%). Conclusion: Ear diseases are most common condition in ENT OPD among paediatric age group. Wax, CSOM and ASOM were the three most common ear diseases. J. Nepal Paediatr. Soc. 32(2) 2012 142-145 doi: http://dx.doi.org/10.3126/jnps.v32i2.5673

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