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Studying the placenta can provide information about the mechanistic pathways of pregnancy disease. However, analyzing placental tissues and manipulating placental function in real-time during pregnancy is not feasible. The ex vivo placental perfusion model allows observing important aspects of the physiology and pathology of the placenta, while maintaining its viability and functional integrity, and without causing harm to mother or fetus. In this review, we describe and compare setups for this technically complex model and summarize outcomes from various published studies. We hope that our review will encourage wider use of ex vivo placental perfusion, which in turn would generate more knowledge to improve pregnancy outcomes.

Exposure of blood to a foreign surface in the form of a diagnostic or therapeutic biomaterial device or implanted cells or tissue elicits an immediate, evolutionarily conserved thromboinflammatory response from the host. Primarily designed to protect against invading organisms after an injury, this innate response features instantaneous activation of several blood-borne, highly interactive, well-orchestrated cascades and cellular events that limit bleeding, destroy and eliminate the foreign substance or cells, and promote healing and a return to homeostasis via delicately balanced regenerative processes. In the setting of blood-contacting synthetic or natural biomaterials and implantation of foreign cells or tissues, innate responses are robust, albeit highly context specific. Unfortunately, they tend to be less than adequately regulated by the host’s natural anticoagulant or anti-inflammatory pathways, thereby jeopardizing the functional integrity of the device, as well as the health of the host. Strategies to achieve biocompatibility with a sustained return to homeostasis, particularly while the device remains in situ and functional, continue to elude scientists and clinicians. In this review, some of the complex mechanisms by which biomaterials and cellular transplants provide a “hub” for activation and amplification of coagulation and immunity, thromboinflammation, are discussed, with a view toward the development of innovative means of overcoming the innate challenges.

OBJECTIVE The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma. METHODS The study included all adult patients who underwent first-time glioblastoma surgery in 2012–2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival. RESULTS The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions. CONCLUSIONS Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.

Background Intraoperative neuromonitoring (IONM) techniques have evolved over the past decade into intermittent IONM (I-IONM) and continuous IONM (C-IONM) modes of application. Despite many prior publications on both types of IONM, there remains uncertainty about what outcomes should be measured for each form of IONM. The primary objective of this paper is to define categories of benefit for I-IONM/C-IONM and to clarify and standardize their reporting outcomes. Methods Expert review consensus statement utilizing modified Delphi methodology. Results I-IONM provides diagnosis, classification, and prevention of nerve injury through accurate and early nerve identification. C-IONM provides real-time information on nerve functional integrity and thus may prevent some types of nerve injury but cannot assist in nerve localization. Sudden mechanisms of nerve injury cannot be predicted or prevented by either technique. Conclusions I-IONM and C-IONM are complementary techniques. Future studies evaluating the utility of IONM should focus on outcomes that are appropriate to the type of IONM being utilized.

Cox protein plays a critical role in deciding the lytic-lysogenic switch of P2 enteric phages. This phenomenon makes Cox protein one of the most important candidates in developing novel phage-based...

The integrity of the plasma membrane (MP) and the acrosome (MA) have been two of the most studied seminal evaluation parameters due to their role as a cell boundary and because they are responsible for interactions between cells effective. To assessing more objectively the effects of osmotic stress on the integrity of the PM and MA, as well as the rate of change that occurred during seminal cryopreservation, five freshly collected ejaculates were evaluated, refrigerated at 5 ºC and thawed per ram/session during 5 consecutive weeks. Using eosin-nigrosin (EN) staining, vitality (VIT), morpho abnormalities and cellular response were evaluated after performing osmotic resistance (ORT) and endosmosis (HOST) tests. The direct effect of anysosmosis and cryopreservation on the dependent variables were analyzed using the GLM procedure (SAS®) and when differences were observed, the effects were quantified using the LSMEANS. All the sperm quality values studied were significantly affected (P

Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signals the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We have reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insights on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

Introduction Diabetes has become a global epidemic. Hearing loss has been long associated with diabetes. Brainstem Evoked Response Audiometry (BERA) is an objective, non-invasive, electro diagnostic test that not only evaluates the functional integrity of the subcortical auditory pathway but also provides topo-diagnosis of hearing loss. This study aims to identify the role BERA in detecting hearing loss early in diabetic patients.Materials and Methods In this study a total of 210 patients were taken and subjected to blood glucose levels followed by PTA were divided into two groups. Group I (n=105) consisted of diabetic patients with sensorineural hearing loss (SNHL) and Group II (n=105) had age and sex matched non-diabetics with SNHL. All the patients were evaluated with BERA.Results All the patients were subjected to Brain Stem Evoked Response Audiometry (BERA). Absolute latency of Wave I, III, V, I-III, III-V and I-V were assessed for both the ears. In both ear Absolute latency were significantly higher in diabetics as compared to non-diabetic patientsConclusion The findings of present study showed that the severity of hearing loss was significantly higher in diabetic patients as compared to non-diabetic controls. Level of glycemic control showed a possible link with severity of hearing loss.

Chronic stress causes dendritic atrophy of neurons within the hippocampus and medial prefrontal cortex. In this report, we show that chronic stress leads to reduced long-term potentiation in the pathway from the hippocampus to the medial prefrontal cortex of rats; and that such reduction is rescued by enriched housing environment. Connectivity between the hippocampus and medial prefrontal cortex is proposed to be an essential substrate that is often compromised in several psychiatric disorders. Our observations suggest that a short period of complexity in the housing environment has the potential to protect the functional integrity of this important connection. Ministry of Education (MOE) This study is supported by the Ministry of Education, Singapore (# RG 46/12) to RM.

The human brain is a complex organ with multiple competing imperatives. It must perceive and interpret the world, incorporate new information, and maintain its functional integrity over the lifespan. Neural activity is associated with all of these processes. Spontaneous BOLD signals have been invoked as representing neural activity associated with all of these processes. However, their exact role in these processes remains controversial. Here, we review learning machine theory, molecular mechanisms of synaptic plasticity and homeostasis, and recent experimental evidence to suggest that spontaneous BOLD activity may be more closely aligned with off-line plasticity and homeostatic processes than on-line fluctuations in cognitive content.

To explore how the different types of intraoperative neuromonitoring (IONM)—namely intermittent (I-IONM) and continuous (C-IONM)—differ from each other and to examine how these differences can affect expected outcomes from IONM. Intraoperative neuromonitoring (IONM) is an important surgical tool for assessment of nerve functional status during surgical procedures where a particular nerve is at risk of injury. IONM has evolved especially in the thyroid/parathyroid surgical space. Accurate use of IONM is dependent on correct set-up of the monitoring equipment and on the surgeon’s implementation and responsiveness to the information provided by the equipment. I-IONM and C-IONM are complementary and together facilitate an unparalleled window into intraoperative neural functional integrity. Rate of nerve palsy is not the only outcome to consider when designing a study to define the utility of IONM in surgery. Other outcomes that are important to consider include alterations in surgical decision making based on IONM data including staged surgical approaches and enhanced localization abilities (especially important for I-IONM techniques); temporal course of a nerve injury (especially important for C-IONM); and changes in surgical technique over time induced by intraoperative nerve functional feedback (especially important for C-IONM). The surgical team should be realistic about what they wish to achieve with IONM and choose the form IONM to be used based on these requirements.

Heavy metal (HM) accumulation in the agricultural soil and its toxicity is a major threat for plant growth and development. HMs disrupt functional integrity of the plants, induces altered phenological and physiological responses and slashes down qualitative crop yield. Chemical messengers such as phytohormones, plant growth regulators and gasotransmitters play a crucial role in regulating plant growth and development under metal toxicity in plants. Understanding the intricate network of these chemical messengers as well as interactions of genes/metabolites/proteins associated with HM toxicity in plants is necessary for deciphering insights into the regulatory circuit involved in HM tolerance. The present review describes (a) the role of chemical messengers in HM-induced toxicity mitigation, (b) possible crosstalk between phytohormones and other signaling cascades involved in plants HM tolerance and (c) the recent advancements in biotechnological interventions including genetic engineering, genome editing and omics approaches to provide a step ahead in making of improved plant against HM toxicities.

The wounds which fail to progress through a timely sequence of repair or that proceed through the wound healing process without restoring anatomic and functional integrity are referred as chronic non-healing wounds. This study was conducted on a 50-year old male patient with a painful non-healing ulcer on the medial malleolus of the left lower limb caused by the use of hot water bag during harsh winter in Srinagar. The size of the wound was 2x2 cm on assessing the wound profile. The wound was treated with the application of an ointment made with the combination of powder of Astragalus sarcocolla and Honey in equal amounts. The ointment was applied twice a day on the wound for 20 days. After 7 days of daily application, there was a considerable reduction in the size of wound and significant improvement in other symptoms like pain and tenderness. The ulcer was completely healed in a time period of 21 days. The present case reports that, the ointment prepared with Astragalus sarcocolla and Honey is a cost effective treatment for chronic non-healing wound.

Background CIEDs have historically restricted the use of MRI due to the potential clinical and configurational risks associated with electromagnetic interference. In this study, the authors investigated the impact of Magnetic Resonance Imaging (MRI) on the functional integrity of non-conditional cardiovascular implantable electronic devices (CIEDs) and their clinical correlates. Methods In this prospective, observational single-center study, we enrolled patients undergoing MRI over a 5-year period. Prior to assessing the impact of MRI on CIEDs, we performed interrogations in sequential duplication to assess the intrinsic variability of devices. Subsequently, we performed interrogations immediately after MRI, and monitored changes in device parameters and clinical events. Results We completed 492 MRI studies, 58% in patients with permanent pacemakers (PPMs) and 42% with implantable cardioverter defibrillators (ICDs). Subsequent MRI exposures occurred in 15% encounters. Accounting for intrinsic variability in CIED leads, there were no significant changes in RA, RV, or LV parameters after MRI, regardless of the region imaged (thoracic vs non-thoracic), type of CIED (PPMs vs ICDs) and among those with serial MRIs. When ranked for % change pre- to post-MRI, the majority of RA, RV and LV metrics for thresholds, sensing, and impedance conformed to ≤20% change from baseline. No significant clinical adverse cardiac events or effect on device microcircuitry occurred during the study. Conclusion Incorporating a novel reproducibility tactic, there were neither clinically meaningful device parameter changes nor adverse clinical events during or following MRIs, suggesting the effects of MRI on non-conditional CIED integrity are far less than previously perceived. This article is protected by copyright. All rights reserved.

Background Gymnema sylvestre is a reputable medicinal plant commonly explore for the management of diabetes and other ailments in traditional medicine. In the present study, we investigated the phytochemical compositions and effect of crude extract, hexane, and ethyl-acetate fractions of Gymnema sylvestre on biochemical and hematological parameters of Wistar rats. Methods Albino rats were distributed randomly into a control group and nine treatment groups orally administered crude extract and fractions of Gymnema sylvestre (100, 300, and 600 mg/kg BW) for 21 days. Liver and kidney function indices, as well as hematological parameters, were monitored. Results Our results revealed that the crude methanol extract contains flavonoids (8.56 ± 0.50 mg/g), alkaloids (13.84 ± 0.67 mg/g), total phenol (1.98 ± 0.50 mg/g), saponins (23.85 ± 0.35 mg/g) and tannins (16.00 ± 0.34 mg/g). The crude methanol, ethyl acetate and n-hexane fractions of Gymnema sylvestre had LD50 greater than 5000 mg/kg BW in acute oral toxicity test. The extract and fractions at 300 and 600 mg/kg BW cause loss of body weight of the rats, significantly altered (p p > 0.05) alterations to the levels of biochemical and hematological parameters when compared with the non-treated control. Conclusion Gymnema sylvestre at sub-acute doses of 300 and 600 mg/kg BW could compromise the functional integrity of the rats’ liver and kidney. The study, therefore, suggested the use of Gymnema sylvestre for oral remedy at a dose of 100 mg/kg or below.

Objectives Optimizing valve implantation depth (ID) plays a crucial role in minimizing conduction disturbances and achieving optimal functional integrity. Until now, the impact of intraprocedural fast (FP) or rapid ventricular pacing (RP) on the implantation depth has not been investigated. Therefore, we aimed to (1) evaluate the impact of different pacing maneuvers on ID, and (2) identify the independent predictors of deep ID. Methods 473 TAVR patients with newer-generation self-expanding devices were retrospectively enrolled and one-to-one propensity-score-matching was performed, resulting in a matching of 189 FP and RP patients in each cohort. The final ID was analyzed, and the underlying functional, anatomical, and procedural conditions were evaluated by univariate and multivariate analysis. Results The highest ID was reached under RP in severe aortic valve calcification and valve size 26 mm. Multivariate analysis identified left ventricular outflow (LVOT) calcification [OR 0.50 (0.31–0.81) p = 0.005*], a “flare” aortic root [OR 0.42 (0.25–0.71), p = 0.001*], and RP (OR 0.49 [0.30–0.79], p = 0.004*) as independent highly preventable predictors of a deep ID. In a model of protective factors, ID was significantly reduced with the number of protective criteria (0–2 criteria: − 5.7 mm ± 2.6 vs. 3–4 criteria − 4.3 mm ± 2.0; p Conclusion Data from this retrospective analysis indicate that RP is an independent predictor to reach a higher implantation depth using self-expanding devices. Randomized studies should prove for validation compared to fast and non-pacing maneuvers during valve delivery and their impact on implantation depth. Trail registration Clinical Trial registration: NCT01805739. Graphic abstract Study design: Evaluation of the impact of different pacing maneuvers (fast ventricular pacing—FP vs. rapid ventricular pacing—RP) on implantation depth (ID). After one-to-one-propensity-score-matching, independent protective and risk factors for a very deep ID beneath 6 mm toward the LVOT (®. AVC aortic valve calcification.

a). PURPOSE: Confocal microscopy and aethesiometry have allowed clinicians to assess the structural and functional integrity of corneal nerves in health and disease. This review summarizes literature on nerves in dry eye disease (DED) and discusses how this data can be applied to DED diagnosis and treatment. b). RECENT FINDINGS: Subjects with DED have a heterogenous symptom and sign profile along with variability in nerve structure and function. Most studies have reported lower nerve density and sensitivity in aqueous tear deficiency, while findings are more inconsistent for other DED subtypes. Examining nerve status, along with profiling symptoms and signs of disease, can help categorize subjects into disease phenotypes (structural and functional patterns) that exist under the umbrella of DED. This, in turn, can guide therapeutic decision-making. c). SUMMARY: Due to the heterogeneity in symptoms and signs of DED, corneal nerve evaluations can be valuable for categorizing individuals into disease sub-types and for guiding clinical decision making.

Ensuring the integrity of the recurrent laryngeal nerve (RLN), the external branch of superior laryngeal nerve (EBSLN) and preservation of normal voice are the prime 'functional' goals of thyroid surgery. More in-depth knowledge of neuronal mechanisms has revealed that anatomical integrity does not always translate into functional integrity. Despite meticulous dissection, neural injuries are not always predictable or visually evident. Intraoperative nerve monitoring (IONM) is designed to aid in nerve identification and early detection of functional impairment. With the evolution of technique, intermittent monitoring has given way to continuous-IONM. Over the years, IONM gathered both support and flak. Despite numerous randomised studies, systematic reviews, and meta-analyses, there still prevails a state of clinical equipoise concerning the utility of IONM and its cost-effectiveness. This article inspects the true usefulness of IONM, elaborates on the optimal way to practice it, and presents a critical literature review.

This work aimed to establish whether the temperature humidity index (THI) under different intertropical zones affects the retention of cytoplasmic droplets (CDs), sperm function and DNA integrity in boars. With this purpose, two separate studies were devised. In the first one, 49 boars from six farms were collected every 45 days (230 ejaculates). THI were measured daily, and sperm parameters were evaluated. Boars were classified into three groups based on the incidence of ejaculates having more than 25% spermatozoa with CDs: persistent (at least three consecutive ejaculates), moderate (less than three ejaculates) and absent (no ejaculate having ≥25% spermatozoa with CDs). Farms were classified based on THI through cluster analysis into two groups. In the second study, 32 liquid-stored semen samples were classified based on three cluster analysis: low and high incidence of proximal (PCDs), distal (DCDs) CDs and a combination of PCD and DCDs. high THI farms presented significantly (p < .05) higher proportions of boars with moderate and persistent incidence of CD than those with low THI. In study 2, the presence of PCDs was negatively correlated with sperm DNA integrity (r = -0.691; p < .01). However, differences between groups were more apparent when ejaculates were classified based on both PCDs and DCDs than when PCDs or DCDs were considered separately. In conclusion, classification of boars according to the severity and persistence of CDs in boars allows understanding more clearly the dynamics of CD retention and the effects of ambient temperature and relative humidity. Additionally, the joint analysis of both PCDs and DCDs is necessary in routine sperm quality analyses.

Background Detrimental drug toxicity and failure in efficacy during clinical trials is one of the major hurdles faced by the pharmaceutical companies. Conventionally, preclinical safety evaluation is performed in 2D cell cultures and animal models. However, the response of a drug seen in laboratory animals and cells grown as monolayers differs from how cells inside a human body respond. This is due to the lack of multi-organ interaction in cell cultures and species specificity between animal and human. Scope and approach Recently, progress in organ-on-a-chip (OoC) including multi-organ-on-a-chip (MoC) platform offers fast and cost-effective alternative approach to screen drugs authentically. Advanced human-on-a-chip (HoC) consists of several human organs held together in a hierarchical and physiological pattern crafting an in vitro human model. HoC recapitulates the structural and functional integrity of human system and overcomes the limitations of traditional protocols and inaccessibility to human models. Key findings In HoC, cells are cultured in a sterile controlled environment that allows manipulation of physico-chemical factors, monitoring molecular and functional aspects in a more realistic environment. It also upgrades the knowledge on pharmacokinetics and pharmacodynamics of compounds. There is no doubt that HoC technology is a game changer that will revolutionize clinical research in the upcoming years. This review explains the evolution of OoC to HoC, their potential use and limitations. More emphasis has been given on the potential use of HoC in pharmacology. Conclusions Pharmaceutical companies, academic institutions and regulatory agencies should initiate a joint venture to launch and utilize the full potential of HoC technology as a next generation alternative to preclinical or disease modelling studies.

The glomerular endothelium produces the key complement regulator factor H (FH), but its role in the endothelial cells protection and functional integrity is unclear. In this edition of Kidney International, Mahajan et al. demonstrate that the endothelial-intrinsic FH is important for the cytoskeletal architecture, monolayer integrity, proliferation control, metabolism, and inflammatory signaling regulation. These findings place the endothelium-derived FH in the center of the pathological process of diseases, characterized with FH genetic abnormalities.

The aim of the study is to assess the restoration of anatomical and functional integrity of the uterus and identify changes in hormonal profile in women after laparoscopic and abdominal myomectomy. Material and methods. 58 patients aged 36,2 5,9 years old with uterine myoma underwent myomectomy: 31 patients underwent laparoscopic myomectomy and 27 patients underwent abdominal myomectomy. The selection of surgical approach didnt depend on the size, the number and localization of uterine myomas and the patients concomitant pathology. The hormonal profile of the patients including AMH level was assessed befor myomectomy and in the 6 months after the operation. Postoperative assessment was performed on day 5th8th after surgery and in 1 and 6 months after myomectomy. Results. No significant differences were found in the processes of reparation of the uterus and in hormonal profile of the patients after laparoscopic or abdominal myomectomy. The time required for the patients reabilitation and for the restoration of the ovarian function and uterine morphological structure was similar in both groups. Conclusion. The hormonal profile of the patients and the anatomical and functional restoration of myometrium after myomectomy doesnt depend on the surgical approach if myomectomy is performed by an experienced surgeon after the correct assessment of the clinical situation.

Background: It has been reported that the incidence of recurrent laryngeal nerve (RLN) injury is higher in an operational procedure in the thyroid and parathyroid region. Elevating voice pitch is achieved by the cricothyroid contraction, which in turn is innervated by the external branch of the superior laryngeal nerve (EBSLN). Due to the subtle nature and clinical variability of EBSLN damage, diagnosis may be difficult. The use of intraoperative neuromonitoring (IONM) as a supplement to enhance surgical identification in thyroid and parathyroid operation appeared to have collected momentum with operators. Methods: IONM clinical usage rationale, efficiency, and safety profile are discussed in this overview in thyroid and parathyroid surgery. Results: IONM usage incurred numerous skepticisms in decreasing the frequency of EBSLN or RLN injury. However, a recent article has shown the efficacy and benefits of using IONM in thyroid and parathyroid procedures. IONM facilitates the recognition of RLN and EBSLN, verifies its functional integrity, localizes the site of a nerve injury, and gives postsurgical function feedback. This technique has been successful in reducing rates of bilateral laryngeal paralysis, with the elevated safety profile for surgical patients. Conclusions: It is recommended using IONM in all thyroidectomies and in high-risk parathyroidectomies.

Summary Background Coronavirus disease 2019 has stretched the ability of many institutions to supply needed personal protective equipment, especially N95 respirators. N95 decontamination and re-use programmes provide one potential solution to this problem. Unfortunately, a comprehensive evaluation of the effects of decontamination on the fit of various N95 models using a quantitative fit test (QNFT) approach is lacking. Aims To investigate the effects of up to eight rounds of vaporized hydrogen peroxide (VHP) decontamination on the fit of N95 respirators currently in use in a hospital setting, and to examine if N95 respirators worn by one user can adapt to the face shape of a second user with no compromise to fit following VHP decontamination. Methods The PortaCount Pro+ Respirator Fit Tester Model 8038 was used to quantitatively define functional integrity, measured by fit, of N95 respirators following decontamination with VHP. Findings There was an observable downward trend in the functional integrity of Halyard Fluidshield 46727 N95 respirators throughout eight cycles of decontamination with VHP. Functional integrity of 3M 1870 N95 respirators was reduced significantly after the respirator was worn, decontaminated with VHP, and then quantitatively fit tested on a second user. Furthermore, inconsistencies between qualitative fit test and QNFT results were uncovered that may have strong implications on the fit testing method used by institutions. Conclusions The data revealed variability in the functional integrity of different N95 models after VHP decontamination, and exposed potential limitations of N95 decontamination and re-use programmes.

The tumor suppressor protein p53 is a master regulator of cell fate. The activity of p53 is controlled by a plethora of posttranslational modifications (PTMs). However, despite extensive research, the mechanisms of this regulation are still poorly understood due to a paucity of biochemical studies with p53 carrying defined PTMs. Here, we report a protein semi-synthesis approach to access site-specifically modified p53. We synthesized a set of chemically homogeneous full-length p53 carrying one (Ser20ph and Ser15ph) or two (Ser15,20ph) naturally occurring, damage-associated phosphoryl marks. Refolding and biochemical characterization of semisynthetic p53 variants confirmed their structural and functional integrity. Furthermore, we show that phosphorylation within the N-terminal domain directly enhances p300-dependent acetylation approximately twofold, consistent with the role of these marks in p53 activation. Given that the p53 N-terminus is a hotspot for PTMs, we believe that our approach will contribute greatly to a mechanistic understanding of how p53 is controlled by PTMs., ‘Designer’ p53: semi-synthesis of the tumor suppressor protein p53 via native chemical ligation enables in vitro structure–activity studies to reveal how this master regulator of cell fate is itself regulated by phosphorylation.

The blood-brain barrier (BBB) is a physical structure whose main function is to strictly regulate access to circulating compounds into the central nervous system (CNS). Vegetable-derived phenolic compounds have been widely studied, with numerous epidemiologic and interventional studies confirming their health-related bioactivities across multiple cells, organs and models. Phenolics are non-essential xenobiotics, and should theoretically be unable to cross the BBB. The present work summarizes current experimental evidence that reveals that not only are phenolic compounds able to cross the BBB and bioaccumulate in the brain, but there is some stereoselectivity, which suggests the presence of specific transporters that allow them to reach the brain. Some molecules cross the BBB intact, while others do so only after being biotransformed or metabolized elsewhere. Once inside the CNS, they prevent or counter oxidative stress, which maintains the molecular, cellular, structural and functional integrity of the brain, and subsequently, overall human health.

Geomorphological zoning is as an integrated approach to analyze the land surface and subsequently synthesize the spatial analysis with geomorphological processes developed on it. The main types and objectives of geomorphological zoning are discussed within the framework of a . geomorphologic region , or a modeled geomorphic system. The geomorphological zoning approach is based on understanding of system-wide and geographical laws of the structural and functional integrity of spatial objects within the system. At the same time, the identity of geomorphological region is connected to its internal make-up- element, integrity, structure, stability, dynamics, genesis, and with functioning – transformation of solar energy, moisture circulation, geochemical circulation, biological metabolism, mechanical movement of material under the action of gravity. The main approaches available to date to geomorphological zoning are considered. The main principles of geomorphological zoning are formulated. The conclusion is made about the fundamental possibility of geomorphological zoning in accordance with the stated principles and its, first of all, practical orientation.

Enterocutaneous fistulae (ECFs) are commonly encountered complications in medical and surgical practice. High-output fistulae are associated with significant morbidity and mortality, poor quality of life, and a substantial healthcare burden. An interdisciplinary team approach is crucial to prevent and mitigate the adverse clinical consequences of high-output ECFs including sepsis, metabolic derangements, and malnutrition. Patients with ECFs are at a significantly higher risk of developing malnutrition and close monitoring by nutrition support professionals and/or a nutrition support team is an essential component of their medical management. High-output ECFs often require the initiation of nutrition support through either enteral or parenteral routes. Historically, parenteral nutrition (PN) has been the primary method of nutrition support in these patients. However, oral and enteral nutrition (EN) should remain viable options if an evaluation of the location of the ECF, amount of remaining functional bowel, and volume of ECF output identifies favorable conditions. Additionally, in contrast to PN, oral nutrition and EN are the preferred method of feeding because of the maintenance of the structural and functional integrity of the gastrointestinal tract. The inclusion of pharmacological interventions can greatly assist with the reduction and stabilization of ECF output and thereby permit sustained enteral feeding. Initiation of supplemental or full PN will be required if oral nutrition and EN lead to metabolic derangements, fail to meet energy requirements, or do not maintain or improve the patient's nutrition status. The main focus of this review is to discuss the nutrition management of patients with high-output ECFs.