Platypnea orthodeoxia syndrome in a patient with patent foramen ovale and normal atrial pressure. Case report and presentation of underlying pathophysiological mechanisms

Platypnea-orthodeoxia Syndrome is characterized by clinically significant postural hypoxia. The full spectrum of the syndrome includes intracardial and extracardial abnormalities with R->L shunt. Various concurrent underlying physiological abnormalities are usually encountered that require thorough clinical and laboratory evaluation. A high clinical suspicion in patients with unexplained dyspnea is also required to reach a firm diagnosis. We herein present a rare case of an 82-years-old patient with episodic unexplained dyspnea, patent foramen ovale with normal pulmonary pressures and we review the underlying physiologic mechanisms.

An integrated approach to the pathogenetic therapy of constipation

The data on the causes of defecation disorders, mechanisms of normal defecation, and pathogenetic aspects of constipation are presented. Functional gastrointestinal disorders are considered as a common pathology of the gastrointestinal tract, which is based on combined morphological and physiological abnormalities associated with visceral hypersensitivity, disorders of gastrointestinal motility, protective mucous barrier, immune function and the composition of the intestinal microbiota. The article discusses the possibility of using the drinking medicinal mineral water Zajecicka Horka (Zayechitskaya bitter) for intestinal pathology and other functional gastrointestinal disorders.

GC-MS Analysis and Antimicrobial Activities of Ethanol Alkaloid Leaf Extracts of Delonix elata.L

Delonix elata L., belongs to family Fabaceae used by the traditional various medicinal practices to cure jaundice, skin disease, heart disease, cancer cell formation, physiological abnormalities, heptoprotective, bronchial and rheumatic problems. The present study was screen the antimicrobial and phytochemical activity of alkaloid leaf extracts. This extracts was assessed on multidrug resistant clinical isolated from both gram positive, gram negative and antifungal strains including Bacillus subtilis, Staphylococcus aureus, Escherchia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. The zone of inhibition was determined by Agar well diffusion method with various concentration. GC- MS analysis was performed to identify major bioactive compounds present in the extracts. The GC – MS studies shown the present of 25 compound were identified in the leaf extract composition. The antimicrobial analysis revealed that C. albicans showed a highest zone of inhibition 25mm at 100 mg/ml of extracts. Present finding suggest that D. elata as plant pharmaceutical and pharmacological importance.

COMPUTER HYBRID SYSTEM OF HEMORRHAGE (HES) DETECTION USED FOR AIDED DIAGNOSIS OF DIABETIC RETINOPATHY

Diabetes cause’s metabolic and physiological abnormalities in the retina and the changes suggest a role for inflammation in the development of diabetic retinopathy. Abnormal blood vessels can form in the back of the eye of a person with diabetes. These new blood vessels are weaker and prone to breaking and causing hemorrhage (HEs). Diabetic retinopathy (DR) accounts for 31.5–54% of all cases of vitreous hemorrhage in adults in the world. Therefore, detection of HEs is still a challenging factor task for computer-aided diagnostics of DR. Many researchers have developed advanced algorithms of hemorrhages detection using fundus images. In this paper, a robust and computationally efficient approach for HEs with different shape and size detection and classification is presented. First, brightness correction and contrast enhancement are applied to fundus images. Second, candidate hemorrhages are extracted by using an unsupervised classification algorithm. Third, an approach based on mathematical morphology is carried out for vascular network and macula segmentation. Finally, a total of 13 HEs features are considered in this study and selected for classification. The proposed method is evaluated on 419 fundus images of DIARETDB0, DIARETDB1 and MESSIDOR databases. Experimental results show that overall average sensitivity, specificity, predictive value and accuracy for hemorrhage in lesion level are 98.90%, 99.66%, 97.63% and 99.56%, respectively. The results show that the proposed method outperforms other state-of-the-art methods in detection of hemorrhages. These results indicate that this new method may improve the performance of diagnosis of DR system.

RHEB/mTOR hyperactivity causes cortical malformations and epileptic seizures through increased axonal connectivity

Hyperactivation of the mammalian target of rapamycin (mTOR) pathway can cause malformation of cortical development (MCD) with associated epilepsy and intellectual disability (ID) through a yet unknown mechanism. Here, we made use of the recently identified dominant-active mutation in Ras Homolog Enriched in Brain 1 (RHEB), RHEBp.P37L, to gain insight in the mechanism underlying the epilepsy caused by hyperactivation of the mTOR pathway. Focal expression of RHEBp.P37L in mouse somatosensory cortex (SScx) results in an MCD-like phenotype, with increased mTOR signaling, ectopic localization of neurons, and reliable generalized seizures. We show that in this model, the mTOR-dependent seizures are caused by enhanced axonal connectivity, causing hyperexcitability of distally connected neurons. Indeed, blocking axonal vesicle release from the RHEBp.P37L neurons alone completely stopped the seizures and normalized the hyperexcitability of the distally connected neurons. These results provide new evidence of the extent of anatomical and physiological abnormalities caused by mTOR hyperactivity, beyond local malformations, which can lead to generalized epilepsy.

Minute ventilation/carbon dioxide production in patients with dysfunctional breathing

Dysfunctional breathing refers to a multi-dimensional condition that is characterised by pathological changes in an individual's breathing. These changes lead to a feeling of breathlessness and include alterations in the biomechanical, psychological and physiological aspects of breathing. This makes dysfunctional breathing a hard condition to diagnose, given the diversity of aspects that contribute to the feeling of breathlessness. The disorder can debilitate individuals without any health problems, but may also be present in those with underlying cardiopulmonary co-morbidities. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. This review will explore how this single measurement can be used to aid the diagnosis of dysfunctional breathing. A background discussion about dysfunctional breathing will allow readers to comprehend its multidimensional aspects. This will then allow readers to understand how VeqCO2 can be used in the wider diagnosis of dysfunctional breathing. Whilst VeqCO2 cannot be used as a singular parameter in the diagnosis of dysfunctional breathing, this review supports its use within a broader algorithm to detect physiological abnormalities in patients with dysfunctional breathing. This will allow for more individuals to be accurately diagnosed and appropriately managed.

I overthink—therefore I am not: Altered Sense of Self in Depersonalisation Disorder

This paper considers the phenomenology of depersonalisation disorder, in relation to predictive processing and its associated pathophysiology. To do this, we first establish a few mechanistic tenets of predictive processing that are necessary to talk about phenomenal transparency, mental action, and self as subject. We briefly review the important role of ‘predicting precision’ and how this affords mental action and the loss of phenomenal transparency. We then turn to sensory attenuation and the phenomenal consequences of (pathophysiological) failures to attenuate or modulate sensory precision. We then consider this failure in the context of depersonalisation disorder. The key idea here is that depersonalisation disorder reflects the remarkable capacity to explain perceptual engagement with the world via the hypothesis that “I am an embodied perceiver, but I am not in control of my perception”. We suggest that individuals with depersonalisation may believe that ‘another agent’ is controlling their thoughts, perceptions or actions, while maintaining full insight that the ‘another agent’ is ‘me’ (the self). Finally, we rehearse the predictions of this formal analysis, with a special focus on the psychophysical and physiological abnormalities that may underwrite the phenomenology of depersonalisation.

Preexisting Dementia Is Associated with Increased Risks of Mortality and Morbidity Following Major Surgery: A Nationwide Propensity Score Matching Study

Patients with dementia are predisposed to multiple physiological abnormalities. It is uncertain if dementia associates with higher rates of perioperative mortality and morbidity. We used reimbursement claims data of Taiwan’s National Health Insurance and conducted propensity score matching analyses to evaluate the risk of mortality and major complications in patients with or without dementia undergoing major surgery between 2004 and 2013. We applied multivariable logistic regressions to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the outcome of interest. After matching to demographic and clinical covariates, 7863 matched pairs were selected for analysis. Dementia was significantly associated with greater risks of 30-day in-hospital mortality (aOR: 1.71, 95% CI: 1.09–2.70), pneumonia (aOR: 1.48, 95% CI: 1.16–1.88), urinary tract infection (aOR: 1.59, 95% CI: 1.30–1.96), and sepsis (OR: 1.77, 95% CI: 1.34–2.34) compared to non-dementia controls. The mortality risk in dementia patients was attenuated but persisted over time, 180 days (aOR: 1.49, 95% CI: 1.23–1.81) and 365 days (aOR: 1.52, 95% CI: 1.30–1.78) after surgery. Additionally, patients with dementia were more likely to receive blood transfusion (aOR: 1.32, 95% CI: 1.11–1.58) and to need intensive care (aOR: 1.40, 95% CI: 1.12–1.76) compared to non-dementia controls. Senile dementia and Alzheimer’s disease were independently associated with higher rates of perioperative mortality and complications, but vascular dementia was not affected. We found that preexisting dementia was associated with mortality and morbidity after major surgery.

Consecutive intra-gingival injections of lipopolysaccharide and butyric acid to mice induce abnormal behavior and changes in cytokine concentrations

Background Periodontopathic bacteria such as Porphyromonas gingivalis produce several metabolites, including lipopolysaccharide (LPS) and n-butyric acid (BA). Past work suggested that periodontal infection may cause cognitive impairment in mice. Aims To elucidate the mechanisms by which metabolites such as LPS and BA, resulting from Porphyromonas gingivalis activity, induce immunological and physiological abnormalities in mice. Methods In the present work, 28 male ICR mice were placed in an open-field arena and the total distance (cm/600 s) they covered was recorded. Based on their moving distances, mice were divided into 4 groups (n = 7) and injected the following substances into their gingival tissues for 32 consecutive days: saline (C), 5 mmol/L of BA (B), 1 μg/mouse of LPS (L), and BA-LPS (BL) solutions. Distances covered by mice were also measured on days 14 and 21, with their habituation scores considered as “(moving distance on day 14 or 21)/(moving distance on day 0)”. Afterwards, mice were dissected, and hippocampal gene expression and the concentrations of short-chain fatty acids, neurotransmitters and cytokines in their blood plasma and brains were analyzed. In addition, mouse brain and liver tissues were fixed and visually assessed for histopathological abnormalities. Results Group BL had significantly higher habituation scores than C and B on day 14. LPS induced higher habituation scores on day 21. LPS induced significant decreases in the mRNA levels of interleukin (IL)-6 and brain-derived neurotrophic factors, and an increase in neurotrophic tyrosine kinase receptor type 2. In both plasma and brain, LPS induced a significant acetate increase. Moreover, LPS significantly increased acetylcholine in brain. In plasma alone, LPS and BA significantly decreased monocyte chemoattractant protein 1 (MCP-1). However, while LPS significantly decreased tyrosine, BA significantly increased it. Lastly, LPS significantly decreased IL-6 and tumor necrosis factor in plasma. No histopathological abnormalities were detected in liver or brain tissues of mice. Conclusion We showed that injections of LPS and/or BA induced mice to move seemingly tireless and that both LPS and BA injections strongly induced a reduction of MCP-1 in blood plasma. We concluded that LPS and BA may have been crucial to induce and/or aggravate abnormal behavior in mice.