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Article ; Online: Peptides as Potential Therapeutics for Alzheimer's Disease.

Ribarič, Samo

2018 Volume 23, Issue 2

Abstract: ... integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g ... extracellular space, that alters proteostasis and triggers Aβ modification (e.g., by reactive oxygen species (ROS ...

Abstract	Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer's disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic interventions that at best slow-down disease progression. The key biochemical change in AD is the excessive accumulation of per-se non-toxic and soluble amyloid peptides (Aβ(1-37/44), in the intracellular and extracellular space, that alters proteostasis and triggers Aβ modification (e.g., by reactive oxygen species (ROS)) into toxic intermediate, misfolded soluble Aβ peptides, Aβ dimers and Aβ oligomers. The toxic intermediate Aβ products aggregate into progressively less toxic and less soluble protofibrils, fibrils and senile plaques. This review focuses on peptides that inhibit toxic Aβ oligomerization, Aβ aggregation into fibrils, or stabilize Aβ peptides in non-toxic oligomers, and discusses their potential for AD treatment.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/therapeutic use ; Animals ; Humans ; Protein Multimerization/drug effects ; Protein Processing, Post-Translational/drug effects ; Proteostasis/drug effects ; Reactive Oxygen Species/metabolism ; Solubility
Chemical Substances	Amyloid beta-Peptides ; Reactive Oxygen Species
Language	English
Publishing date	2018-01-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules23020283
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Article ; Online: Peptides as Potential Therapeutics for Alzheimer’s Disease

Samo Ribarič

Molecules, Vol 23, Iss 2, p

2018 Volume 283

Abstract	Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer’s disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic interventions that at best slow-down disease progression. The key biochemical change in AD is the excessive accumulation of per-se non-toxic and soluble amyloid peptides (Aβ(1-37/44), in the intracellular and extracellular space, that alters proteostasis and triggers Aβ modification (e.g., by reactive oxygen species (ROS)) into toxic intermediate, misfolded soluble Aβ peptides, Aβ dimers and Aβ oligomers. The toxic intermediate Aβ products aggregate into progressively less toxic and less soluble protofibrils, fibrils and senile plaques. This review focuses on peptides that inhibit toxic Aβ oligomerization, Aβ aggregation into fibrils, or stabilize Aβ peptides in non-toxic oligomers, and discusses their potential for AD treatment.
Keywords	aggregation ; Alzheimer’s disease ; amyloid β oligomers ; amyloid β peptide ; amyloid β plaques ; insulin ; neurofibrillary tangles ; tau protein ; peptides ; peptide therapy ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Diet and aging.

Ribarič, Samo

Oxidative medicine and cellular longevity

2012 Volume 2012, Page(s) 741468

Abstract: ... stress responses at the cellular and whole-organism level by modulating epigenetic mechanisms (e.g., DNA ... e.g., TOR, AMPK, p53, and FOXO), and cell-to-cell signaling molecules (e.g., adiponectin ...

Abstract	Nutrition has important long-term consequences for health that are not only limited to the individual but can be passed on to the next generation. It can contribute to the development and progression of chronic diseases thus effecting life span. Caloric restriction (CR) can extend the average and maximum life span and delay the onset of age-associated changes in many organisms. CR elicits coordinated and adaptive stress responses at the cellular and whole-organism level by modulating epigenetic mechanisms (e.g., DNA methylation, posttranslational histone modifications), signaling pathways that regulate cell growth and aging (e.g., TOR, AMPK, p53, and FOXO), and cell-to-cell signaling molecules (e.g., adiponectin). The overall effect of these adaptive stress responses is an increased resistance to subsequent stress, thus delaying age-related changes and promoting longevity. In human, CR could delay many diseases associated with aging including cancer, diabetes, atherosclerosis, cardiovascular disease, and neurodegenerative diseases. As an alternative to CR, several CR mimetics have been tested on animals and humans. At present, the most promising alternatives to the use of CR in humans seem to be exercise, alone or in combination with reduced calorie intake, and the use of plant-derived polyphenol resveratrol as a food supplement.
MeSH term(s)	Aging/genetics ; Aging/physiology ; Animals ; Caloric Restriction ; Diet ; Epigenesis, Genetic ; Humans ; Nutritional Status
Language	English
Publishing date	2012-08-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2455981-7
ISSN	1942-0994 ; 1942-0994
ISSN (online)	1942-0994
ISSN	1942-0994
DOI	10.1155/2012/741468
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Article ; Online: The pharmacological properties and therapeutic use of apomorphine.

Ribarič, Samo

Molecules (Basel, Switzerland)

2012 Volume 17, Issue 5, Page(s) 5289–5309

Abstract: ... an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides ...

Abstract	Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D₁, D(2S), D(2L), D₃, D₄, and D₅ receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT(1A), 5HT(2A), 5HT(2B), and 5HT(2C)), and α-adrenergic receptors (α(1B), α(1D), α(2A), α(2B), and α(2C)). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (i.e., to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer's disease has been suggested; APO seems to stimulate Aβ catabolism in an animal model and cell culture, thus reducing the rate of Aβ oligomerisation and consequent neural cell death.
MeSH term(s)	Alzheimer Disease/drug therapy ; Animals ; Apomorphine/therapeutic use ; Dogs ; Dopamine Agonists/therapeutic use ; Erectile Dysfunction/drug therapy ; Female ; Humans ; Male ; Parkinson Disease/drug therapy ; Receptors, Adrenergic, alpha/metabolism ; Receptors, Dopamine/metabolism ; Receptors, Serotonin/metabolism ; Substance-Related Disorders/drug therapy
Chemical Substances	Dopamine Agonists ; Receptors, Adrenergic, alpha ; Receptors, Dopamine ; Receptors, Serotonin ; Apomorphine (N21FAR7B4S)
Language	English
Publishing date	2012-05-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules17055289
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Article ; Online: Hidden hazards of SARS-CoV-2 transmission in hospitals: A systematic review.

Ribaric, Noach Leon / Vincent, Charles / Jonitz, Günther / Hellinger, Achim / Ribaric, Goran

Indoor air

2021 Volume 32, Issue 1, Page(s) e12968

Abstract: Despite their considerable prevalence, dynamics of hospital-associated COVID-19 are still not well understood. We assessed the nature and extent of air- and surface-borne SARS-CoV-2 contamination in hospitals to identify hazards of viral dispersal and ... ...

Abstract	Despite their considerable prevalence, dynamics of hospital-associated COVID-19 are still not well understood. We assessed the nature and extent of air- and surface-borne SARS-CoV-2 contamination in hospitals to identify hazards of viral dispersal and enable more precise targeting of infection prevention and control. PubMed, ScienceDirect, Web of Science, Medrxiv, and Biorxiv were searched for relevant articles until June 1, 2021. In total, 51 observational cross-sectional studies comprising 6258 samples were included. SARS-CoV-2 RNA was detected in one in six air and surface samples throughout the hospital and up to 7.62 m away from the nearest patients. The highest detection rates and viral concentrations were reported from patient areas. The most frequently and heavily contaminated types of surfaces comprised air outlets and hospital floors. Viable virus was recovered from the air and fomites. Among size-fractionated air samples, only fine aerosols contained viable virus. Aerosol-generating procedures significantly increased (OR
MeSH term(s)	Air Microbiology ; Air Pollution, Indoor ; COVID-19/transmission ; Cross Infection/transmission ; Cross-Sectional Studies ; Fomites/virology ; Hospitals ; Humans ; Observational Studies as Topic ; SARS-CoV-2
Language	English
Publishing date	2021-12-04
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	1081722-0
ISSN	1600-0668 ; 0905-6947
ISSN (online)	1600-0668
ISSN	0905-6947
DOI	10.1111/ina.12968
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Article ; Online: The Pharmacological Properties and Therapeutic Use of Apomorphine

Samo Ribarič

Molecules, Vol 17, Iss 5, Pp 5289-

2012 Volume 5309

Abstract: ... an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides ...

Abstract	Apomorphine ( APO) is an aporphine derivative used in human and veterinary medicine. APO activates D 1 , D 2S , D 2L , D 3 , D 4 , and D 5 receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT 1A , 5HT 2A , 5HT 2B , and 5HT 2C ), and α-adrenergic receptors (α 1B , α 1D , α 2A , α 2B , and α 2C ). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction ( i.e. , to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer’s disease has been suggested; APO seems to stimulate Ab catabolism in an animal model and cell culture, thus reducing the rate of Ab oligomerisation and consequent neural cell death.
Keywords	apomorphine ; Alzheimer’s disease ; dopamine agonist ; erectile dysfunction ; Parkinson’s disease ; Organic chemistry ; QD241-441
Subject code	290
Language	English
Publishing date	2012-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Simulation of the Frank-Starling Law of the Heart.

Ribarič, Samo / Kordaš, Marjan

Computational and mathematical methods in medicine

2012 Volume 2012, Page(s) 267834

Abstract: ... in cardiovascular variables (e.g., arterial pressure, ventricular volume, and valve flows) if either preload or ...

Abstract	We developed a lumped parameter, computer-based model of an equivalent electronic circuit for a one-atrium one-ventricle (frog) heart attached to a vascular circuit, to simulate a basic concept of cardiovascular physiology, the Frank-Starling Law of the Heart. A series of simulations was performed, to observe changes in cardiovascular variables (e.g., arterial pressure, ventricular volume, and valve flows) if either preload or afterload was increased. The simulated data agreed qualitatively, and quantitatively when experimental data are available, with data obtained on amphibian or on mammalian myocardium. In addition, the data obtained in these simulations improve our understanding of the mechanism(s) whereby the heart muscle adapts itself to increased distension (increased preload) or to impeded systolic contraction (increased afterload). The analysis of the measured valve flows suggests that the ventricle is a highly input sensitive pump because the input pressure determines the diastolic distension and, consequently, the force of ventricular systolic contraction. On the other hand, the ventricle is a relatively output insensitive pump. Therefore, not only atrium contraction, but also predominantly the preceding ventricular systolic contraction is the main mechanism of the subsequent diastolic ventricular filling. We conclude that the presented model enables the study of basic concepts of cardiovascular physiology.
MeSH term(s)	Animals ; Arterial Pressure ; Blood Pressure ; Computational Biology/methods ; Computer Simulation ; Electrophysiology/methods ; Heart/physiology ; Heart Atria/metabolism ; Heart Ventricles/metabolism ; Humans ; Models, Biological ; Models, Cardiovascular ; Myocardial Contraction/physiology ; Myocardium/metabolism ; Pressure ; Ranidae
Language	English
Publishing date	2012-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2252430-7
ISSN	1748-6718 ; 1748-670X ; 1027-3662
ISSN (online)	1748-6718
ISSN	1748-670X ; 1027-3662
DOI	10.1155/2012/267834
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Article ; Online: Quantifying hospital environmental ventilation using carbon dioxide monitoring - a multicentre study.

Wilson, N M / Calabria, C / Warren, A / Finlay, A / O'Donovan, A / Passerello, G L / Ribaric, N L / Ward, P / Gillespie, R / Farrel, R / McNarry, A F / Pan, D

Anaesthesia

2023 Volume 79, Issue 2, Page(s) 147–155

Abstract: The COVID-19 pandemic has highlighted the importance of environmental ventilation in reducing airborne pathogen transmission. Carbon dioxide monitoring is recommended in the community to ensure adequate ventilation. Dynamic measurements of ventilation ... ...

Abstract	The COVID-19 pandemic has highlighted the importance of environmental ventilation in reducing airborne pathogen transmission. Carbon dioxide monitoring is recommended in the community to ensure adequate ventilation. Dynamic measurements of ventilation quantifying human exhaled waste gas accumulation are not conducted routinely in hospitals. Instead, environmental ventilation is allocated using static hourly air change rates. These vary according to the degree of perceived hazard, with the highest change rates reserved for locations where aerosol-generating procedures are performed, where medical/anaesthetic gases are used and where a small number of high-risk infective or immunocompromised patients may be isolated to reduce cross-infection. We aimed to quantify the quality and distribution of ventilation in hospital by measuring carbon dioxide levels in a two-phased prospective observational study. First, under controlled conditions, we validated our method and the relationship between human occupancy, ventilation and carbon dioxide levels using non-dispersive infrared carbon dioxide monitors. We then assessed ventilation quality in patient-occupied (clinical) and staff break and office (non-clinical) areas across two hospitals in Scotland. We selected acute medical and respiratory wards in which patients with COVID-19 are cared for routinely, as well as ICUs and operating theatres where aerosol-generating procedures are performed routinely. Between November and December 2022, 127,680 carbon dioxide measurements were obtained across 32 areas over 8 weeks. Carbon dioxide levels breached the 800 ppm threshold for 14% of the time in non-clinical areas vs. 7% in clinical areas (p < 0.001). In non-clinical areas, carbon dioxide levels were > 800 ppm for 20% of the time in both ICUs and wards, vs. 1% in operating theatres (p < 0.001). In clinical areas, carbon dioxide was > 800 ppm for 16% of the time in wards, vs. 0% in ICUs and operating theatres (p < 0.001). We conclude that staff break, office and clinical areas on acute medical and respiratory wards frequently had inadequate ventilation, potentially increasing the risks of airborne pathogen transmission to staff and patients. Conversely, ventilation was consistently high in the ICU and operating theatre clinical environments. Carbon dioxide monitoring could be used to measure and guide improvements in hospital ventilation.
MeSH term(s)	Humans ; Carbon Dioxide ; Pandemics ; Respiratory Aerosols and Droplets ; Hospitals ; COVID-19
Chemical Substances	Carbon Dioxide (142M471B3J)
Language	English
Publishing date	2023-12-07
Publishing country	England
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	80033-8
ISSN	1365-2044 ; 0003-2409
ISSN (online)	1365-2044
ISSN	0003-2409
DOI	10.1111/anae.16124
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Article ; Online: Gastric band is safe and effective at three years in a national study subgroup of non-morbidly obese patients.

Ribaric, Goran / Buchwald, Jane

Croatian medical journal

2014 Volume 55, Issue 4, Page(s) 405–415

Abstract: Aim: To analyze the 3-year outcomes of lower body mass index (BMI) (<35 kg/m2) adjustable gastric band (AGB) recipients across multiple sites in the French health insurance system.: Methods: From prospectively collected data on a cohort of 517 ... ...

Abstract	Aim: To analyze the 3-year outcomes of lower body mass index (BMI) (<35 kg/m2) adjustable gastric band (AGB) recipients across multiple sites in the French health insurance system. Methods: From prospectively collected data on a cohort of 517 morbidly obese Swedish Adjustable Gastric Band® (SAGB) patients (Clinical Trials Web database, #NCT01183975), a retrospective analysis of a subgroup of 29 low-BMI patients was conducted. Patients had a severe obesity-related comorbidity, had undergone a prior bariatric procedure requiring reintervention, or had a maximum adult BMI≥40. Safety (mortality, adverse events) and effectiveness (BMI change, excess weight loss [EWL, %], total body weight loss [%TBWL], quality of life [QoL], and comorbidities) were evaluated. Results: Multiple surgical teams/sites enrolled patients and performed SAGB procedures between September 2, 2007 and April 30, 2008. Of 29 low-BMI patients (mean age, 41.3±10.3 years), 89.7% were female, and obesity duration was 13.6±7.3 years. Mean BMI was 31.5±3.7; there were 37 comorbidities in 15/29 patients. At 3-year follow-up, BMI was 29.4±4.9 (mean change, -2.3±6.2; P=0.069); total cohort EWL, 7.3±74.8%; TBWL, 6.2±18.8%; BMI≥30 to <35 EWL, 38.8±48.0%; there were 7 comorbidities in 15/29 patients (P<0.031). There were 20 adverse events in 13 patients (44.8%); SAGBs were retained in 25/29 (86.2%) at 3 years. Conclusions: In a retrospective analysis of a subgroup of BMI<35 kg/m2 patients, some following a prior bariatric procedure, SAGB was found to be safe and effective at 3-year follow-up.
MeSH term(s)	Adult ; Body Mass Index ; Comorbidity ; Female ; Follow-Up Studies ; Gastroplasty/adverse effects ; Humans ; Male ; Middle Aged ; Obesity/surgery ; Quality of Life ; Reoperation ; Retrospective Studies ; Weight Loss
Language	English
Publishing date	2014-08-27
Publishing country	Croatia
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1157623-6
ISSN	1332-8166 ; 0353-9504
ISSN (online)	1332-8166
ISSN	0353-9504
DOI	10.3325/cmj.2014.55.405
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Article ; Online: Impact of a digital surgical workflow including Digital Device Briefing Tool on morbidity and mortality in a patient population undergoing primary stapled colorectal anastomosis for benign or malignant colorectal disease: protocol for a multicentre prospective cohort study.

Lauscher, Johannes / Beyer, Katharina / Hellinger, Achim / Croner, Roland S / Ridwelski, Karsten / Krautz, Christian / Lim, Christine / Coplan, Paul M / Kurepkat, Marc / Ribaric, Goran

BMJ open

2023 Volume 13, Issue 3, Page(s) e070053

Abstract: Introduction: With growing emphasis on surgical safety, it appears fundamental to assess the safety of colorectal resection involving primary stapled anastomosis. Surgical stapling devices can considerably foster patient safety in colorectal surgery, ... ...

Abstract	Introduction: With growing emphasis on surgical safety, it appears fundamental to assess the safety of colorectal resection involving primary stapled anastomosis. Surgical stapling devices can considerably foster patient safety in colorectal surgery, but their misuse or malfunction encompass a unique risk of postoperative complications. The Digital Device Briefing Tool (DDBT) is a digital cognitive aid developed to enhance safe use of the Ethicon circular stapling device during colorectal resection. The purpose of this study is to evaluate how a digital operative workflow, including DDBT, compared with routine surgical care, affects morbidity and mortality in patients undergoing left-sided colorectal resection with primary stapled colorectal anastomosis for colorectal cancer or benign disease. Methods and analysis: A multicentre, prospective cohort study will be conducted at five certified academic colorectal centres in Germany. It compares a non-digital with a Johnson & Johnson digital solution (Surgical Process Institute Deutschland (SPI))-guided operative workflow in patients undergoing left hemicolectomy, sigmoidectomy, anterior rectal resection and Hartmann reversal procedure. The sample size is set at 528 cases in total, divided into 3 groups (a non-digital and two SPI-guided workflow cohorts, with and without DDBT) in a ratio of 1:1:1, with 176 patients each. The primary endpoint is a composite outcome comprising the overall rate of surgical complications, including death, during hospitalisation and within the first 30 days after colorectal resection. Secondary endpoints include operating time, length of hospital stay and 30-day hospital readmission rate. Ethics and dissemination: This study will be performed in line with the Declaration of Helsinki. The ethics committee of the Charité-University Medicine Berlin, Germany, approved the study (No: 22-0277-EA2/060/22). Study Investigators will obtain written informed consent from each patient before a patient may participate in this study. The study results will be submitted to an international peer-reviewed journal. Trial registration number: DRKS00029682.
MeSH term(s)	Humans ; Prospective Studies ; Workflow ; Anastomosis, Surgical/methods ; Colonic Diseases/etiology ; Colectomy/adverse effects ; Morbidity ; Colorectal Neoplasms/surgery ; Colorectal Neoplasms/etiology ; Multicenter Studies as Topic
Language	English
Publishing date	2023-03-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-070053
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