Metaproteogenomic analysis of saliva samples from Parkinson's disease patients with cognitive impairment

Cognitive impairment (CI) is very common in patients with Parkinson's Disease (PD) and progressively develops on a spectrum from mild cognitive impairment (PD-MCI) to full dementia (PDD). Identification of PD patients at risk of developing cognitive decline, therefore, is unmet need in the clinic to manage the disease. Previous studies reported that oral microbiota of PD patients was altered even at early stages and poor oral hygiene is associated with dementia. However, data from single modalities are often unable to explain complex chronic diseases in the brain and cannot reliably predict the risk of disease progression. Here, we performed integrative metaproteogenomic characterization of salivary microbiota and tested the hypothesis that biological molecules of saliva and saliva microbiota dynamically shift in association with the progression of cognitive decline and harbor discriminatory key signatures across the spectrum of CI in PD. We recruited a cohort of 115 participants in a multi-center study and employed multi-omics factor analysis (MOFA) to integrate amplicon sequencing and metaproteomic analysis to identify signature taxa and proteins in saliva. Our baseline analyses revealed contrasting interplay between the genus Neisseria and Lactobacillus and Ligilactobacillus genera across the spectrum of CI. The group specific signature profiles enabled us to identify bacterial genera and protein groups associated with CI stages in PD. Our study describes compositional dynamics of saliva across the spectrum of CI in PD and paves the way for developing non-invasive biomarker strategies to predict the risk of CI progression in PD.FEMS Research and Training Gran

Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma

The aim of this study was to evaluate germline variant frequencies of pheochromocytoma and paraganglioma targeted susceptibility genes with next-generation sequencing method. Germline DNA from 75 cases were evaluated with targeted next-generation sequencing on an Illumina NextSeq550 instrument. KIF1B, RET, SDHB, SDHD, TMEM127, and VHL genes were included in the study, and Sanger sequencing was used for verifying the variants. The pathogenic/likely pathogenic variants were in the VHL, RET, SDHB, and SDHD genes, and the diagnosis rate was 24% in this study. Three different novel pathogenic variants were determined in five cases. This is the first study from Turkey, evaluating germline susceptibility genes of pheochromocytoma and paraganglioma with a detection rate of 24% and three novel variants. All patients with pheochromocytoma and paraganglioma need clinical genetic testing with expanded targeted gene panels for higher diagnosis rates

The effects of Covid-19 on physical medicine and rehabilitation in Turkey in the first month of pandemic

Objectives: The outbreak of novel coronavirus-2019 (COVID-19) has affected Turkey very seriously, as well as all around the world. Many urgent and radical measures were taken due to the high contagious risk and mortality rate of the outbreak. It is noteworthy that isolation recommendations and the provision of health services for pandemic have a negative impact on Physical Medicine and Rehabilitation (PMR) services. In this study, we aimed to evaluate the effects of COVID-19 on the PMR services and physiatrists immediately after the first month of pandemic in Turkey. Patients and methods: An online survey consisting of 45 items was sent to the members of the Turkish Society of Physical Medicine and Rehabilitation. The main goal of the survey was to evaluate the changes in the provided service of PMR and conditions of physiatrists one month after the first reported COVID-19 case in Turkey. Results: A total of 606 PMR specialists and residents responded to the survey. The mean number of the patients visited the outpatient clinics was 148.2 +/- 128.5 per week before the pandemic, it significantly decreased to 23.4 +/- 33.1 per week after the first month of the reported first COVID-19 case. Similarly, the mean number of the patients of inpatient service significantly decreased from 21.7 +/- 39.3 per week to 2.5 +/- 10.0 per week after the first month of the pandemic. Most of the residents (69%) reported that their training was seriously affected due to pandemic. From the economic aspect, 69.2% of the participants who were working at private hospitals reported a decrease in their monthly salary, and 21% of them were sent to an unpaid vacation. A total of 21.9% of private-practice institutions paused their services. During the first month, 46.9% of the participants were assigned to the different services such as COVID-19 inpatient service, emergency or COVID-19 outpatient clinics. According to the Republic of Turkey, Ministry of Health guideline and algorithm, 15.7% of the physicians were in the category of healthcare workers with suspected COVID-19. Conclusion: The COVID-19 pandemic affected seriously both the services and the PMR physicians as early as the first month. This effect is expected to become worse, when the duration of pandemic prolongs. Proper arrangements and measures should be planned to ameliorate the negative effects of the pandemic on the patients and PMR physicians

Effects of different frequencies and application regions of repetetive transcranial magnetic stimulation (rTMS) on weight gain and microbiota in healthy mice

Repetatif Manyetik Stimulasyon (rTMS) girişimsel olmayan beyin uyarım yöntemi olup, kafa derisi üzerinde tutulan indüktif bobinden geçen akım etkisiyle meydana gelen manyetik alanın ilgili beyin bölgesindeki nöron topluluğu üzerinde elektrik akım yoğunluğunu uyarmasına dayanmaktadır. rTMS tedavisi, herhangi bir cerrahi işlem içermemesi, uygulama kolaylığı ve güvenirliği sayesinde bir çok nörolojik hastalıkların, obezite ve yeme bozuklukları tedavilerinde kullanılmaktadır. Genel olarak, düşük frekansta (1 Hz ve aşağısı) inhibe edici etki gösterirken, yüksek frekansta (5 Hz ve yukarısı) uyarıcı etki göstermektedir. Mortalite ve morbidite oranları oldukça yüksek olan obezite ve yeme bozukluklarında, rTMS tedavisi klinik uygulamalarda olumlu sonuçlar vermektedir. Klinikte uygulamalara rağmen, yöntemin moleküler ve hücresel etki mekanizması henüz tam olarak aydınlatılamamıştır. Bu sebeple klinik-öncesi çalışmalar ve hayvan deneylerinden elde edilen bilgiler mekanizmanın aydınlatılmasında büyük önem arz etmektedir. Bu çalışmada rTMS'in görülen olumlu etki mekanizmalarına insan mikrobiyomundaki rTMS tedavisindeki değişimlerin katkıda bulunabileceği hipotezini test ettik. rTMS tedavisinin hastalık modeli içermeyen sağlıklı farelerin kilo artışları ve mikrobiyotası üzerindeki etkisi araştırıldı. Manyetik stimulasyon, 1 Hz düşük-frekans ve 20 Hz yüksek-frekansta beyin ve abdominal bölgeye uygulanarak 4 deney grubu oluşturuldu. Kontrol grubu farelere manyetik stimulasyon uygulamadı. TMS-beyin 1 Hz ve TMS-karın 20 Hz gruplarında istatiksel olarak anlamlı kilo azalması saptandı. Bağırsak mikrobiyotası biyoinformatik analizlerine göre TMS-karın 20 Hz grubunda kolon ve ince bağırsak mikrobiyal kompozisyonda anlamlı değişimler bulundu. Frekans ve uygulama bölge farkının daha iyi anlaşılabilmesi için uygulama öncesi ve sonrasında kan testi parametreleriyle metabolik çıktılarla desteklenen ek çalışmalara ihtiyaç vardır.Repetitive magnetic stimulation (rTMS) is a non-invasive brain stimulation method that stimulate neurons via generation of a pulse high intensity magnetic field by passing an electric current through an inductive coil. However, despite the wide application of rTMS in clinical practice, the molecular and cellular mechanisms underlying the method remain uncertain. For this reason, the information obtained from pre-clinical studies and in vitro animal experiments have great importance on the understanding of the mechanism. In general terms, low frequency (LF) rTMS (1 Hz) decreases cortical excitability, whereas high-frequency (HF) rTMS (>5 Hz) increases cortical excitability. rTMS method gives positive results in the treatment of obesity and eating disorders which are associated with high mortality and morbidity rates. Additionally, the microbiota of normal individuals shows significant differences compared to those with obese and eating disorders. In this study, we investigated the effects of different frequencies and application regions of rTMS on weight gain and microbiota in healthy mice. We performed 4 experimental groups, and the magnetic stimulation was applied to the brain and abdominal region at 1 Hz low-frequency and 20 Hz high-frequency. The mice of the control didn't receive stimulation. 20 Hz rTMS-abdominal and 1 Hz rTMS-brain groups showed statistically significant weight reduction. According to bioinformatic analysis of the intestinal microbiota, severe microbial imbalance was detected in the gut colon and intestine fecal samples of the TMS-abdominal group at 20 Hz frequency. In order to better understanding of frequency and application region difference, we need to further investigations which are supported by metabolic outputs and blood test parameters

Metaproteogenomic analysis of saliva samples from Parkinson's disease patients with cognitive impairment

Cognitive impairment (CI) is very common in patients with Parkinson's Disease (PD) and progressively develops on a spectrum from mild cognitive impairment (PD-MCI) to full dementia (PDD). Identification of PD patients at risk of developing cognitive decline, therefore, is unmet need in the clinic to manage the disease. Previous studies reported that oral microbiota of PD patients was altered even at early stages and poor oral hygiene is associated with dementia. However, data from single modalities are often unable to explain complex chronic diseases in the brain and cannot reliably predict the risk of disease progression. Here, we performed integrative metaproteogenomic characterization of salivary microbiota and tested the hypothesis that biological molecules of saliva and saliva microbiota dynamically shift in association with the progression of cognitive decline and harbor discriminatory key signatures across the spectrum of CI in PD. We recruited a cohort of 115 participants in a multi-center study and employed multi-omics factor analysis (MOFA) to integrate amplicon sequencing and metaproteomic analysis to identify signature taxa and proteins in saliva. Our baseline analyses revealed contrasting interplay between the genus Neisseria and Lactobacillus and Ligilactobacillus genera across the spectrum of CI. The group specific signature profiles enabled us to identify bacterial genera and protein groups associated with CI stages in PD. Our study describes compositional dynamics of saliva across the spectrum of CI in PD and paves the way for developing non-invasive biomarker strategies to predict the risk of CI progression in PD