Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.

Importance: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models. Objective: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT. Design, Setting, and Participants: This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis. Intervention: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy. Main Outcomes and Measures: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs). Results: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group. Conclusions and Relevance: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD. Trial Registration: ClinicalTrials.gov Identifier: NCT04854291.

Rare origin of the sinoatrial node artery: an anatomic report and a brief review of the literature.

Several studies reported anatomical variations in the sinoatrial node artery (SANa). Here, we report a rare variation in the origin of the SANa on a human adult male cadaver. During dissection, we identified the SANa originating from a large atrial branch of the right coronary artery (RCA). This branch originates at the level of the inferior border of the heart and courses upwards. The initial part of this vessel is tortuous, and then it follows a straight path parallel to the RCA along the anterior surface of the right atrium. After this part, the artery curves posteriorly and to the left until it reaches the lower border of the right auricle, where it closely approaches the RCA. Finally, the artery runs posteriorly and to the right to follow a course along the medial wall of the right auricle and right atrium to reach a location close to the region of the junction of the superior vena cava and right atrium, where it follows its path buried in the myocardium. After perforating the myocardium, this vessel gives rise to branches that are distributed to both atria in addition to the SANa. The SANa runs to the sinoatrial node in a precaval (anterior to the superior vena cava) course. We also tried to characterize the vessels radiologically. The knowledge of the anatomical variations of the SANa is of the utmost importance for cardiologists and heart surgeons to better understand cardiac disease and accurately plan and execute cardiac interventions and surgical procedures.

High-Caloric Diets in Adolescence Impair Specific GABAergic Subpopulations, Neurogenesis, and Alter Astrocyte Morphology.

We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid (GABA)ergic system, including the Ca2+-binding proteins parvalbumin (PV), calretinin (CR), calbindin (CB), and the neuropeptides somatostatin (SST) and neuropeptide Y (NPY). We also analyzed the density of cholinergic varicosities, brain-derived neurotrophic factor (BDNF), reelin (RELN), and cyclin-dependent kinase-5 (CDK-5) mRNA levels, and glial fibrillary acidic protein (GFAP) expression. The cafeteria diet reduced PV-positive neurons in the granular layer, hilus, and CA1, as well as NPY-positive neurons in the hilus, without altering other GABAergic populations or overall GABA levels. The high-sugar diet induced a decrease in the number of PV-positive cells in CA3 and an increase in CB-positive cells in the hilus and CA1. No alterations were observed in the cholinergic varicosities. The cafeteria diet also reduced the relative mRNA expression of RELN without significant changes in BDNF and CDK5 levels. The cafeteria diet increased the number but reduced the length of the astrocyte processes. These data highlight the significance of determining the mechanisms mediating the observed effects of these diets and imply that the cognitive impairments previously found might be related to both the neuroinflammation process and the reduction in PV, NPY, and RELN expression in the hippocampal formation.

Lateral rectus pulley concerning the orbital wall. Area of a stereotyped bony insertion.

Purpose: To examine the lateral rectus muscle pulley and its bony insertion concerning the orbital rim and periorbita. Design: Prospective. An observational anatomic study. Methods: Study population: Twenty postmortem orbits (10 right, 10 left) of 10 Caucasian cadavers (8 females, 2 males; age range at death, 57-100 years; median age, 79.5 years) fixed by the Thiel method.Intervention: The floor of the temporal fossa was exposed, and a bone window on the lateral wall of the orbit, posterior to the sphenozygomatic suture, was created, keeping the periorbita intact. The lateral canthus and lateral palpebral ligament were isolated and opened, and the eyelids were folded back. The frontozygomatic suture was identified, and the orbital septum opened adjacent to the orbital rim. The conjunctiva was opened at the limbus, and the lateral rectus insertion was isolated. The bone pillar containing the frontozygomatic suture and the insertion of the periorbita and the pulley was isolated and removed en bloc. The lateral rectus muscle was isolated and excised.Main outcome measures: Position of the pulley ring on the lateral rectus muscle belly and its bony attachment area in the lateral wall of the orbit. Results: The pulley bony attachment was roughly quadrilateral with an approximate area of 90 mm2, 3 mm (mean, range 1-5 mm) posteroinferior to the frontozygomatic suture and 1 mm posterior to the orbital rim. The anterior margin of the pulley sleeve was found at 21.0 mm (median, p25-75 20.0-22.8) from the scleral insertion. Conclusions: The lateral rectus pulley is stereotyped in its position in the muscle belly and its bony insertion, coinciding with the point of greatest adhesion of the periorbita to the anterior part of the lateral wall of the orbit.

Effects of Aging and Nerve Growth Factor on Neuropeptide Expression and Cholinergic Innervation of the Rat Basolateral Amygdala.

The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.

Superior Gluteal Nerve Anatomy and Its Injuries: Aiming for a More Secure Surgical Approach of the Pelvic Region.

Because most of the recognized causes of superior gluteal nerve (SGN) injury are iatrogenic, detailed knowledge of the anatomy of the SGN is crucial to prevent its injury associated with surgical procedures. This study aims to describe the precise location of SGN or its branches at the greater sciatic foramen, measure the distances of these neural structures to palpable bony landmarks, and evaluate the possible correlation between these parameters and pelvis size. Twenty human cadaveric hemipelvises were studied. After dissection to expose the SGN or its branches at the greater sciatic foramen, the distances from these neural structures to the greater trochanter (GT), to the anterior superior iliac spine (ASIS), to the posterior superior iliac spine (PSIS), to the ischial tuberosity (IT), and to the greater sciatic notch apex were measured. We found that at the greater sciatic foramen, the SGN emerges as a common trunk in 75% of hemipelvises, and already divided in its superior and inferior branches in 25% of hemipelvises. When the SGN exits the pelvis as a common trunk, it does so, in most cases, in contact with the bone at the apex of the greater sciatic notch or superior to the level of the apex. The median distance from the SGN at the greater sciatic notch to the PSIS, ASIS, GT and IT is 7.6 cm, 10.9 cm, 7.5 cm and 10.8 cm, respectively. We found a positive correlation between some of the analyzed parameters and the size of the pelvis. The anatomical data of this study may serve as pivotal guides during orthopedic pelvic surgery, contributing to minimize SNG iatrogenic lesions with significant implications in the patient's quality of life.

Effects of High-Fat and High-Fat High-Sugar Diets in the Anxiety, Learning and Memory, and in the Hippocampus Neurogenesis and Neuroinflammation of Aged Rats.

High-caloric diets induce several deleterious alterations in the human body, including the brain. However, information on the effects of these diets on the elderly brain is scarce. Therefore, we studied the effects of 2 months of treatment with high-fat (HF) and high-fat-high-sugar (HFHS) diets on aged male Wistar rats at 18 months. Anxiety levels were analyzed using the open-field and plus-maze tests, while learning and memory processes were analyzed using the Morris water maze test. We also analyzed neurogenesis using doublecortin (DCX) and neuroinflammation using glial fibrillary acidic protein (GFAP). In aged rats, the HFHS diet impaired spatial learning, memory, and working memory and increased anxiety levels, associated with a reduction in the number of DCX cells and an increase in GFAP cells in the hippocampus. In contrast, the effects of the HF diet were lighter, impairing spatial memory and working memory, and associated with a reduction in DCX cells in the hippocampus. Thus, our results suggest that aged rats are highly susceptible to high-caloric diets, even if they only started in the elderly, with an impact on cognition and emotions. Furthermore, diets rich in saturated fats and sugar are more detrimental to aged rats than high-fat diets are.

Fecal microbiome alterations in treatment-naive de novo Parkinson's disease.

Gut microbiota alterations in Parkinson's disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.

The Surgical Vascular Anatomy of the Lower Lumbar Arteries and Its Implications in Minimally Invasive Spine Surgery: A Cadaveric Study.

BACKGROUND: Minimally invasive lateral lumbar interbody fusion is a technique that has become increasingly popular for the treatment of degenerative lumbar spine disease; however, the pertinent surgical vascular anatomy has not been examined in detail. The goal of this study is to examine the anatomy of the lower lumbar and median sacral arteries, which are important determinants of these surgical outcomes. METHODS: This is an observational, experimental study based on cadaveric models, including 20 embalmed adult human cadavers. The following measurements were made: length of the lumbar and median sacral arteries, vertical distance between the third and fourth lumbar arteries and the superior end plate of the corresponding vertebrae, anterior vertebral body height, and intervertebral disc height. RESULTS: Our sample showcased considerable variability regarding vascular anatomy around the lower lumbar spine. In 10% of specimens, the abdominal aorta bifurcated at the level of the L3-L4 intervertebral disc, and 20% showed variations in vena cava origin. Regarding the lumbar arteries, in 10% of the sample, the fourth lumbar artery was absent on the right side, and 10% presented a fifth lumbar artery. The median sacral artery was present in all cadavers; however, in 15% of specimens, it originated from a common trunk that also gave rise to the fourth pair of lumbar arteries. Anterior vertebral body height was smaller in L3 comparing with L5 (P = 0.003), and there was a significant cephalocaudal increase in the anterior intervertebral disc height in the analyzed levels (P < 0.001). Bilaterally, the distance between the fourth lumbar arteries and the superior end plate of the L4 vertebral body was shorter than this distance at the L3 vertebral body (P < 0.001 and P = 0.002 on the right and left, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: These data may be useful in spine surgery planning and operative management. These anatomic variations should be identified beforehand to prevent difficulties during surgery and possible complications.

Bacterial Butyrate in Parkinson's Disease Is Linked to Epigenetic Changes and Depressive Symptoms.

BACKGROUND: The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers. OBJECTIVES: Here, we investigate whether the changes in the gut microbiome and associated metabolites are related to PD symptoms and epigenetic markers in leucocytes and neurons. METHODS: Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified genome-wide DNA methylation by targeted bisulfite sequencing. RESULTS: We show that lower fecal butyrate and reduced counts of genera Roseburia, Romboutsia, and Prevotella are related to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA regions in PD overlap with those altered in gastrointestinal (GI), autoimmune, and psychiatric diseases. CONCLUSIONS: Decreased levels of bacterially produced butyrate are related to epigenetic changes in leucocytes and neurons from PD patients and to the severity of their depressive symptoms. PD shares common butyrate-dependent epigenetic changes with certain GI and psychiatric disorders, which could be relevant for their epidemiological relation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson's disease.

We aimed to investigate the link between serum metabolites, gut bacterial community composition, and clinical variables in Parkinson's disease (PD) and healthy control subjects (HC). A total of 124 subjects were part of the study (63 PD patients and 61 HC subjects). 139 metabolite features were found to be predictive between the PD and Control groups. No associations were found between metabolite features and within-PD clinical variables. The results suggest alterations in serum metabolite profiles in PD, and the results of correlation analysis between metabolite features and microbiota suggest that several bacterial taxa are associated with altered lipid and energy metabolism in PD.

Behavioral and brain morphological analysis of non-inflammatory and inflammatory rat models of preterm brain injury.

Investigations using preclinical models of preterm birth have much contributed, together with human neuropathological studies, for advances in our understanding of preterm brain injury. Here, we evaluated whether the neurodevelopmental and behavioral consequences of preterm birth induced by a non-inflammatory model of preterm birth using mifepristone would differ from those after inflammatory prenatal transient hypoxia-ischemia (TSHI) model. Pregnant Wistar rats were either injected with mifepristone, and pups were delivered on embryonic day 21 (ED21 group), or laparotomized on the 18th day of gestation for 60 min of uterine arteries occlusion. Rat pups were tested postnatally for characterization of developmental milestones and, after weaning, they were behaviorally tested for anxiety and for spatial learning and memory. One month later, brains were processed for quantification of doublecortin (DCX)- and neuropeptide Y (NPY)-immunoreactive cells, and cholinergic varicosities in the hippocampus. ED21 rats did not differ from controls with respect to neonatal developmental milestones, anxiety, learning and memory functions, and neurochemical parameters. Conversely, in TSHI rats the development of neonatal reflexes was delayed, the levels of anxiety were reduced, and spatial learning and memory was impaired; in the hippocampus, the total number of DCX and NPY cells was increased, and the density of cholinergic varicosities was reduced. With these results we suggest that a preterm birth, in a non-inflammatory prenatal environment, does not significantly change neonatal development and adult neurologic outcome. On other hand, prenatal hypoxia and ischemia (inflammation) modifies developmental trajectory, learning and memory, neurogenesis, and NPY GABAergic and cholinergic brain systems.

Effects of aging on the cholinergic innervation of the rat ventral tegmental area: A stereological study.

Dopamine neurons in the ventral tegmental area (VTA) play a main role in processing both rewarding and aversive stimuli, and their response to salient stimuli is significantly shaped by afferents originating in the brainstem cholinergic nuclei. Aging is associated with a decline in dopaminergic activity and reduced response to positive reinforcement. We have used stereological techniques to examine, in adult and aged rats, the dopaminergic neurons and the cholinergic innervation of the VTA, and the cholinergic populations of the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei, which are the only source of cholinergic inputs to the VTA. In the VTA, there were no age-related variations in the number and size of tyrosine hydroxylase (TH)-immunoreactive neurons, but the density of cholinergic varicosities was reduced in aged rats. The total number of choline acetyltransferase (ChAT)-immunoreactive neurons in the PPT and LDT was unchanged, but their somas were hypertrophied in aged rats. Our results suggest that dysfunction of the cholinergic system might contribute for the age-associated deterioration of the brain reward system.

Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease.

BACKGROUND: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson's disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. METHODS: Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. RESULTS: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1ß in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. CONCLUSIONS: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.

Surgical anatomy of the radial nerve in the arm: a cadaver study.

PURPOSE: The purpose of this study was to analyse the anatomic course of the radial nerve (RN) in the arm, in order to minimize the potential risk of surgical injury. METHODS: The study was performed in 19 embalmed upper extremities of 11 adult human cadavers. We measured: distance from deltoid insertion (DI) into the humerus to lateral epicondyle (LE); distance from RN piercing point into the lateral intermuscular septum (LIS) to three other points-DI, LE and RN division into superficial and deep terminal branches; distance between the LE and the RN division. To assess variability, we correlated the distances between the landmarks to the overall length of the arm. RESULTS: The RN was found to pierce the LIS within 31.6 mm of the most distal DI into the humerus. The mean distance between the entry point of RN in the LIS and the LE was 107.2 mm. The mean distance between RN perforating point in the LIS and RN division in its terminal branches was 86.4 mm. The DI-LE and the LIS-LE showed a moderate positive correlation with the length of the arm. CONCLUSION: We describe the DI relationship to the RN course and also report its proportion within overall arm length which has not been previously described. Using the arm length as reference, our results show that RN can be found to perforate on the LIS at a point distal to the DI by 11% and proximal to the LE by 38%.

Adhesive dentistry sensory stimulus technique as a neuromechanism for the treatment of orofacial pain associated to temporomandibular disorders: Case study.

PURPOSE: The authors intend, by presenting a case study, emphasize the neuromodulation process of orofacial pain induced by the stimulation of the sensory and motor stimulation of the trigeminal nerve, which can play an important role on pain modulation. MATERIALS AND METHODS: A 25 year-old woman presenting orofacial pain was referred to the stomatology service at the Centro Hospitalar do Porto. After collecting the patient's anamnesis, the thermographic camera FLIR i7 was used to record the thermal status of the orofacial structures, before the adhesive dentistry sensory stimulus protocol, after 45 minutes, and after one week. RESULTS: This study suggests the relation of adhesive dentistry sensory stimulus technique in the neuromodulation of orofacial pain and its association with the temporomandibular disorders . As the tongue senses the stimulus of the resin composite placed on the palatal surface of the 1st premolar, 2nd premolar and 1st molar of the maxilla, this can promote and induce an effect regarding a peripheral nerve neuromodulation resulting in a blockage of the nociceptive trigeminal pathway from temporomandibular disorders. CONCLUSION: Orofacial pain is a common complaint among the patients that come to a dentistry appointment, which may have different diagnosis and treatments. A positive effect on the patient's symptomatology was confirmed clinically on subsequent dental appointments and monitored by infrared thermography.

Effects of chronic alcohol consumption and withdrawal on the cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei of the rat: An unbiased stereological study.

The brain cholinergic system comprises two main recognized subdivisions, the basal forebrain and the brainstem cholinergic systems. The effects of chronic alcohol consumption on the basal forebrain cholinergic nuclei have been investigated extensively, but there is only one study that has examined those effects on the brainstem cholinergic nuclei. The last one comprises the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei, which are known to give origin to the main cholinergic projection to the ventral tegmental area, a key brain region of the neural circuit, the mesocorticolimbic system, that mediates several behavioral and physiological processes, including reward. In the present study, we have examined, using stereological methods, the effects of chronic alcohol consumption (6 months) and subsequent withdrawal (2 months) on the total number and size of PPT and LDT choline acetyltransferase (ChAT)-immunoreactive neurons. The total number of PPT and LDT ChAT-immunoreactive neurons was unchanged in ethanol-treated and withdrawn rats. However, ChAT-immunoreactive neurons were significantly hypertrophied in ethanol-treated rats, an alteration that did not revert 2 months after ethanol withdrawal. These results show that prolonged exposure to ethanol leads to long-lasting, and potentially irreversible, cytoarchitectonic and neurochemical alterations in the brainstem cholinergic nuclei. These alterations suggest that the alcohol-induced changes in the brainstem cholinergic nuclei might play a role in the mechanisms underlying the development of addictive behavior to alcohol.

Neurosurgical anatomy of the insular cortex.

OBJECTIVE: The purpose of this study was to clarify the morphology of the insular cortex focusing not only on the shape of the insula, but also on sulcal and gyral organization. PATIENTS AND METHODS: Sixty formalin-fixed adult brain hemispheres had their insula exposed and photographed. The dimensions of each gyrus and sulcus were measured using an image analysis software. The morphometric data obtained was statistically analysed. RESULTS: The insular cortex shape alternates between triangular and trapezoid, being the triangular shape the most common (75%). The angle between the posterior and inferior peri-insular sulcus in the trapezoid insulae had a mean range of 131.17° (SD = 12.277). A minimum of 3 and a maximum of 6 insular gyri were observed, being 5 the most common total number of gyri observed. The accessory gyrus was present in 66% of the insulae and well-developed in 38% of the cases. A statistical association between the number of gyri in the posterior lobe and the presence of a novel gyrus or a more developed accessory gyrus in the anterior lobe was found (P = 0.006). The posterior short gyrus was the longest of the short gyri (P <  0.001), followed by the anterior short gyrus (P < 0.001). The anterior long gyrus was the largest of the long gyri (P = 0.003). The contribution of each of the short gyri to the formation of the insular apex was inconstant. The most common observed apex arrangement was the combination of the anterior and of the middle short gyri. CONCLUSIONS: This study makes a strong contribution to the understanding of the insular cortex anatomy, allowing neurosurgeons to be more capable to decide the best approach to this cortical area.

Increasing Comparability and Utility of Gut Microbiome Studies in Parkinson's Disease: A Systematic Review.

Gut microbiota have been studied in relation to the pathophysiology of Parkinson's disease (PD) due to the early gastrointestinal symptomatology and presence of alpha-synuclein pathology in the enteric nervous system, hypothesized to ascend via the vagal nerve to the central nervous system. Accordingly, sixteen human case-control studies have published gut microbiome composition changes in PD and reported over 100 differentially abundant taxa covering all taxonomic levels from phylum to genus or species, depending on methodology. While certain findings were replicated across several studies, various contradictory findings were reported. Here, differences in methodologies and the presence of possible confounders in the study populations are assessed for their potential to confound the results of gut microbiome studies in PD. Gut microbiome studies in PD exhibited considerable variability with respect to the study population, sample transport conditions, laboratory protocols and sequencing, bioinformatics pipelines, and biostatistical methods. To move from the current heterogeneous dataset towards clinically relevant biomarkers and the identification of putative therapeutic targets, recommendations are derived from the limitations of the available studies to increase the future comparability of microbiome studies in PD. In addition, integration of currently available data on the gut microbiome in PD is proposed to identify robust gut microbiome profiles in PD. Furthermore, expansion of the current dataset with atypical parkinsonism cohorts, prodromal and treatment-naïve de novo PD subjects, measurements of fecal microbial concentrations and multi-omics assessments are required to provide clinically relevant biomarkers and reveal therapeutic targets within the gut microbiome of PD.

gapFinisher: A reliable gap filling pipeline for SSPACE-LongRead scaffolder output.

Unknown sequences, or gaps, are present in many published genomes across public databases. Gap filling is an important finishing step in de novo genome assembly, especially in large genomes. The gap filling problem is nontrivial and while there are many computational tools partially solving the problem, several have shortcomings as to the reliability and correctness of the output, i.e. the gap filled draft genome. SSPACE-LongRead is a scaffolding tool that utilizes long reads from multiple third-generation sequencing platforms in finding links between contigs and combining them. The long reads potentially contain sequence information to fill the gaps created in the scaffolding, but SSPACE-LongRead currently lacks this functionality. We present an automated pipeline called gapFinisher to process SSPACE-LongRead output to fill gaps after the scaffolding. gapFinisher is based on the controlled use of a previously published gap filling tool FGAP and works on all standard Linux/UNIX command lines. We compare the performance of gapFinisher against two other published gap filling tools PBJelly and GMcloser. We conclude that gapFinisher can fill gaps in draft genomes quickly and reliably. In addition, the serial design of gapFinisher makes it scale well from prokaryote genomes to larger genomes with no increase in the computational footprint.