The pregnancy outcomes among women receiving individualized algorithm dosing with follitropin delta: a systematic review of randomized controlled trials.

PURPOSE: To investigate whether the ovarian stimulation with follitropin delta in an individualized algorithm-based manner is inferior to recombinant human-follicle stimulating's follitropin alfa or follitropin beta conventional dosing regarding a series of established primary endpoints. METHODS: We conducted a registered systematic review (CRD42024512792) on PubMed-MEDLINE, Web of Science™, Cochrane Database of Systematic Reviews, and Scopus. Our search was designed to cover all relevant literature, particularly randomized controlled trials. We critically and comparatively analyzed the outcomes for each primary endpoint based on the intervention, reflected by the positive ßhCG test, clinical pregnancy, vital pregnancy, ongoing pregnancy, live birth, live birth at 4 weeks, and multiple pregnancies. RESULTS: Six randomized controlled trials were included in the quality assessment as priority manuscripts, revealing an 83.3% low risk of bias. Follitropin delta led to non-significant differences in each parameter of interest from positive ßhCG test (691; 53.44% vs. 602; 46.55%), ongoing pregnancies (603; 53.79% vs. 518; 46.20%), clinical and vital pregnancies (1,073; 52.80% vs. 959; 47.19%), to live birth and at 4 weeks (595; 54.14% vs. 504; 45.85%) with only 2 losses, and even multiple pregnancies (8; 66.66% vs. 4; 33.33%). However, follitropin delta was well-tolerated among hypo- and hyper-responders without significant risk of ovarian hyperstimulation syndrome and/or preventive interventions in contrast with follitropin alfa or follitropin beta. CONCLUSION: The personalized individualized-based algorithm dosing with follitropin delta is non-inferior to conventional follitropin alfa or follitropin beta. It is as effective in promoting a similar response in women without significant comparable adverse effects.

Real-World Utilization of Corticosteroids in Severe Alcoholic Hepatitis: Eligibility, Response, and Outcomes.

Background and Objectives: Alcoholic hepatitis (AH) poses a medical challenge, causing moderately severe to life-threatening episodes with high short- and long-term mortality. This study aimed to explore real-world corticosteroid utilization in severe AH, response predictors, and patient outcomes. Materials and Methods: We conducted a retrospective study on patients admitted for severe AH, defined as a Maddrey Discriminant Function score equal to or above 32, at a tertiary care center. We reviewed patients' medical observation charts to identify corticosteroid prescriptions, reasons for ineligibility, and response rates. Responders were defined based on the Lille score, and predictors of non-response were identified. Short-term (one-month) and long-term (one-year) mortality rates were calculated according to treatment and response. Results: Out of 310 patients enrolled with severe AH, 59% received corticosteroids, achieving a response rate of 75.4%. The reasons for not administering corticosteroids were as follows: uncontrolled infections (27.6%), renal dysfunction (20.4%), gastrointestinal bleeding (18.9%), acute pancreatitis (7.1%), uncontrolled diabetes (3.1%), and other or unknown causes (22.8%). The overall 1-month mortality rate was 12.2%, higher in non-responders (35.3%) and patients who did not receive corticosteroids (13.4%) compared to responders (3.6%). The overall 1-year mortality rate was 62.5%, similar between patients who did not receive corticosteroids (78.7%) and non-responders (77.7%) and higher compared to responders (42.8%). Predictive factors for non-response included older age (OR = 1.05, 95%CI: 1.01-1.08), concomitant cirrhosis (OR= 2.11, 95% CI: 1.064-4.20), MELD scores exceeding 30 (OR = 2.42, 95% CI: 1.21-4.80), severe hypoalbuminemia (OR = 2.46, 95%CI: 1.12-5.37), and increased serum creatinine (OR = 1.5, 95% CI: 1.1-2.03). Among the prognostic scores, MELD 3.0 score exhibited superior efficacy for short-term (AUC = 0.734, 95% CI 0.656-0.811) and long-term mortality (AUC = 0.777, 95% CI: 0.724-0.830) compared to alternative scoring systems. Conclusions: Low eligibility rate and poor prognosis underscore the need for effective therapies. Our findings contribute to refining risk stratification and early prediction of non-response, aiding clinicians in identifying more beneficial therapies.

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Preliminary Data on Gastrointestinal Deficiencies Incidence and the Prevalence of Anxiety During the COVID-19 Pandemic Among the Medical Workers.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious new ß-coronavirus that primarily affects the lungs. Because of its unprecedented spread, in a relatively short interval, it is declared a global pandemic. Binding to the angiotensin-converting enzyme 2 receptors, SARS-CoV-2 is easily disseminated through air. Apart from the established clinical panel, individuals exposed to prolonged chronic stress also manifest gastrointestinal (GI) symptoms similar to those exhibited by SARS-CoV-2-infected patients.The present study aims to assess the incidence of GI deficiencies and prevalence of anxiety among healthy medical staff by applying the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS) and Hamilton Anxiety Rating Scale (HAM-A) during this global crisis.We found significant differences on several items of the VAS-IBS: regarding the incidence of diarrhea (p = 0.04), bloating/gases (p = 0.02), and nausea/vomiting (p = 0.01) from the physical spectrum. After stratification based on age of the participants and after we applied Kruskal-Wallis test because of heterogeneity between groups, we noted two situations in which the null hypothesis is rejected: nausea/vomiting in women between 20 and 30 years, and between 30 and 40, and between 40 and 50 years, respectively (p = 0.026/0.029). Anxiety was prevalent among young and middle-class people after the centralization of HAM-A data, where 40.4% of the participants had various forms of anxiety: mild (n = 13; 13.82%), severe (n = 13; 13.82%), and moderate (n = 12; 12.76%).This study demonstrates that VAS-IBS is a reliable tool for assessing the incidence of GI deficiencies, as well as HAM-A for anxiety.

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.

Comprehensive Review Regarding Mercury Poisoning and Its Complex Involvement in Alzheimer's Disease.

Mercury (Hg) is considered one of the most widespread toxic environmental pollutants, which seems to have multiple effects on organisms even at low concentrations. It has a critical role in many health problems with harmful consequences, with Hg primarily targeting the brain and its components, such as the central nervous system (CNS). Hg exposure was associated with numerous CNS disorders that frequently trigger Alzheimer's disease (AD). Patients with AD have higher concentrations of Hg in blood and brain tissue. This paper aims to emphasize a correlation between Hg and AD based on the known literature in the occupational field. The outcome shows that all these concerning elements could get attributed to Hg. However, recent studies did not investigate the molecular level of Hg exposure in AD. The present review highlights the interactions between Hg and AD in neuronal degenerations, apoptosis, autophagy, oxidative stress (OS), mitochondrial malfunctions, gastrointestinal (GI) microflora, infertility and altering gene expression.

A Retrospective Narrative Mini-Review Regarding the Seminal Microbiota in Infertile Male.

Background: Infertility is a global burden that affects both sexes with the male component remaining as an explored yet crucial research field that might offer novel evidence. Material and Methods: The present narrative mini-review aims to summarize all existing literature regarding the composition of the seminal microflora in infertile men. We performed searches in PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect between 2018 and 2022 using a combination of keywords. Results: A total of n = 33 studies met the eligibility criteria and were further considered. From this, n = 14 were conducted on human patients, n = 3 on zebrafish (Danio rerio), n = 5 on rats, and n = 11 on mice. In twenty-five out of thirty-three papers, the authors sequenced the 16S rRNA; situations occurred where researchers focused on standard laboratory protocols. Lactobacillus and Bifidobacterium are widely recognized as putative beneficial lactic bacteria. These two entities are capable of restoring the host's eubiosis to some extent, blocking pathogens' proliferation and endotoxins, and even alleviating specific patterns encountered in disease(s) (e.g., obesity, type 1 diabetes) due to prolonged exposure to toxicants in adults or from a developmental stage. Over the years, distinct approaches have been perfected, such as the transfer of feces between two species or conventional rudimentary products with proven efficiency. Conclusions: The seminal microflora is decisive and able to modulate psychological and physiological responses. Each individual possesses a personalized microbial profile further shaped by exogenous factors, regardless of sex and species.

The Very First Romanian Unruptured 13-Weeks Gestation Tubal Ectopic Pregnancy.

Tubal ectopic pregnancies remain a challenging and life-threatening obstetric condition in the early stages that unavoidably lead to abortion or rupture, further reflected by the associated maternal mortality. Therefore, in the present case report, we report the experience of a 36-year-old woman who presented to our Emergency Department with a history of moderate hypogastric pain, mild vaginal bleeding, and bilateral mastalgia, symptoms that started 20 days ago after uterine curettage for a declarative eight-week pregnancy. On admission, a physical examination showed regular standard signs. The ultrasound examination revealed in the left abdominal flank a gestational sac with a live fetus corresponding to the gestational age of 13 weeks. Given the position of the gestational sac, we suspected a possible abdominal pregnancy. Independently on her human chorionic gonadotropin (hCG) of 33.980 mIU/mL and hemoglobin (Hb) of 13.4 g/dL, the exact location of the pregnancy following ultrasound was hard to establish. Magnetic resonance imaging (MRI) examination was requested, after which we suspected the diagnosis of ovarian pregnancy. Given the paraclinical and clinical context of the worsening of painful symptoms, we decided to perform an exploratory laparoscopy in the multidisciplinary team (digestive and vascular surgeon) that showed the existence of a tubal pregnancy.

Follitropin Delta as a State-of-the-Art Incorporated Companion for Assisted Reproductive Procedures: A Two Year Observational Study.

Background and objectives: The latest reports suggest that follitropin delta is a highly efficient recombinant human follicle-stimulating hormone (r-hFSH) that became a part of the current assisted reproductive technologies (ARTs). Therefore, the present study aims to assess a series of parameters (follicles, oocytes, and embryos) and further by the outcomes in women following the administration of follitropin delta. Materials and methods: This observational study included 205 women. They were aged between 21 and 43 years (mean 33.45) and an anti-Müllerian hormone (AMH) level ranging from 0.11 to 16.00 ng/dL (mean 2.89). Results: In accordance with the established methodology and following the centralization of data, a total of fifty-eight pregnancies (28.29%) were achieved; forty-five (36.88%) were achieved in women under 35 years and thirteen (15.66%) in women above 35 years. These figures are positively correlated with women's age considering that the number of follicles >18 mm, oocytes fertilized and embryo(s) varies among groups. Regarding the interest parameters, we noted n = 1719 follicles > 18 mm, n = 1279 retrieved oocytes, and n = 677 embryos at day 3. On the other hand, the following figures have been registered in women above 35 years: 814-follicles > 18 mm, 612 oocytes retrieved and 301 embryos at day 3. During this study, we registered only three cases of abortions (n = 1-0.81% in women under 35 years and n = 2-2.40% in women above 35 years). Nine pregnancies (7.37%) were stopped from evolution in females under 35 years, and twelve pregnancies (n = 8-6.55% in women under 35 years, while n = 4 in women above 35 years) were unsuccessful. A twin pregnancy has been confirmed (1.20%) in women above 35 years, six ongoing pregnancies (4.91%) in those under 35 years, and two in both groups (one per group-n = 1-0.81%, and 1.20%-n = 1) in which we did not know the exact result were registered at the end of the established studied interval. However, there were also situations in which the treatment cause an over-reactivity or had no effect; n = 2 were non-responders, and n = 1 exhibited moderate ovarian hyperstimulation syndrome (OHSS). Conclusions: Based on our results, we strongly encourage the use of this recombinant gonadotropin on a much larger scale.

The Prevalence of Ureaplasma Urealyticum and Mycoplasma Hominis Infections in Infertile Patients in the Northeast Region of Romania.

Background and objectives: Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) are two commensal microorganisms that form the urogenital microbiota. Under a state of dysbiosis, both bacteria cause intrauterine infection. Material and methods: Therefore, the purpose of the present study was to analyze the prevalence of UU and MH among four hundred and eleven infertile women. Results: Women between thirty and thirty-five years old were the most affected group, followed by those that were 25 and 30 years old, respectively. Cumulatively, the prevalence of single UU and MH, and coinfection, was 28.46% (n = 117), (n = 2) 0.48%, and 2.91% (n = 12), respectively, with an overall detection rate of 31.87% (n = 131). To assess the associated drug susceptibility, endocervical samples were unequally sent to Regina Maria (n = 281) and Synevo (n = 130) laboratories for further analyses. Pristinamycin (100% vs. 100%) and Josamycin (100% vs. 98.00%) were the most efficient antibiotics in eradicating UU and MH, several others also displaying a high efficiency, among which can be mentioned Doxycycline (98.23%), Minocycline (96.00%), Tetracycline (96.48% vs. 68.00%), and Erythromycin (70.17% vs. 92.00%). Based on antibiograms, Clarithromycin (88.00%), Roxithromycin (88.00%), Levofloxacin (82.00%), and Azithromycin (78.94%) can be further used in treating such infections. On the other hand, Clindamycin (4.00%) and Ciprofloxacin (12.27% vs. 2.00%) are no longer viable because both UU and MH display an intermediate response towards gained resistance. Interestingly, the efficiency of Ofloxacin (22.79% vs. 60.00%) was conflicting, this possibly suggesting a transient stage to a gradual adaptability of these microorganisms to Ofloxacin. Conclusions: The most susceptible age groups in each case were women that were between twenty and forty years old. It can be concluded that four antibiotics can be safely used for treating UU, MH, or dual infections whose efficiency was over 95%.

Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects.

Vitamin B3, or niacin, is one of the most important compounds of the B-vitamin complex. Recent reports have demonstrated the involvement of vitamin B3 in a number of pivotal functions which ensure that homeostasis is maintained. In addition, the intriguing nature of its synthesis and the underlying mechanism of action of vitamin B3 have encouraged further studies aimed at deepening our understanding of the close link between the exogenous supply of B3 and how it activates dependent enzymes. This crucial role can be attributed to the gut microflora and its ability to shape human behavior and development by mediating the bioavailability of metabolites. Recent studies have indicated a possible interconnection between the novel coronavirus and commensal bacteria. As such, we have attempted to explain how the gastrointestinal deficiencies displayed by SARS-CoV-2-infected patients arise. It seems that the stimulation of a proinflammatory cascade and the production of large amounts of reactive oxygen species culminates in the subsequent loss of host eubiosis. Studies of the relationhip between ROS, SARS-CoV-2, and gut flora are sparse in the current literature. As an integrated component, oxidative stress (OS) has been found to negatively influence host eubiosis, in vitro fertilization outcomes, and oocyte quality, but to act as a sentinel against infections. In conclusion, research suggests that in the future, a healthy diet may be considered a reliable tool for maintaining and optimizing our key internal parameters.

Testing the Accuracy of the ARIMA Models in Forecasting the Spreading of COVID-19 and the Associated Mortality Rate.

Background and objectives: The current pandemic of SARS-CoV-2 has not only changed, but also affected the lives of tens of millions of people around the world in these last nine to ten months. Although the situation is stable to some extent within the developed countries, approximately one million have already died as a consequence of the unique symptomatology that these people displayed. Thus, the need to develop an effective strategy for monitoring, restricting, but especially for predicting the evolution of COVID-19 is urgent, especially in middle-class countries such as Romania. Material and Methods: Therefore, autoregressive integrated moving average (ARIMA) models have been created, aiming to predict the epidemiological course of COVID-19 in Romania by using two statistical software (STATGRAPHICS Centurion (v.18.1.13) and IBM SPSS (v.20.0.0)). To increase the accuracy, we collected data between the established interval (1 March, 31 August) from the official website of the Romanian Government and the World Health Organization. Results: Several ARIMA models were generated from which ARIMA (1,2,1), ARIMA (3,2,2), ARIMA (3,1,3), ARIMA (3,2,2), ARIMA (3,1,3), ARIMA (2,2,2) and ARIMA (1,2,1) were considered the best models. For this, we took into account the lowest value of mean absolute percentage error (MAPE) for March, April, May, June, July, and August (MAPEMarch = 9.3225, MAPEApril = 0.975287, MAPEMay = 0.227675, MAPEJune = 0.161412, MAPEJuly = 0.243285, MAPEAugust = 0.163873, MAPEMarch - August = 2.29175 for STATGRAPHICS Centurion (v.18.1.13) and MAPEMarch = 57.505, MAPEApril = 1.152, MAPEMay = 0.259, MAPEJune = 0.185, MAPEJuly = 0.307, MAPEAugust = 0.194, and MAPEMarch - August = 6.013 for IBM SPSS (v.20.0.0) respectively. Conclusions: This study demonstrates that ARIMA is a useful statistical model for making predictions and provides an idea of the epidemiological status of the country of interest.

Preclinical Considerations about Affective Disorders and Pain: A Broadly Intertwined, yet Often Under-Explored, Relationship Having Major Clinical Implications.

Background: Pain, a distinctive undesirable experience, encompasses several different and fluctuating presentations across varying mood disorders. Therefore, the present narrative review aimed to shed further light on the matter, accounting for both experimental animal models and clinical observations about major depressive disorder (MDD) pathology. Method: Major databases were inquired from inception until April 2016 for records about MDD and pain. Results: Pain and MDD are tightly associated with each other in a bi-directional fashion. Several cross-sectional and retrospective studies indicated a high presence of pain in the context of mood disorders, including MDD (up to 65%), but also increased prevalence rates in the case of mood disorders documented among people with a primary diagnosis of either psychological or somatic pain (prevalence rates exceeding 45%). The clinical implications of these observations suggest the need to account for mood and pain manifestations as a whole rather than distinct entities in order to deliver more effective interventions. Limitations: Narrative review, lack of systematic control groups (e.g., people with the primary diagnosis at review, but not the associated comorbidity as a study) to allow reliable comparisons. Prevalence rates and clinical features associated with pain varied across different studies as corresponding operational definitions did. Conclusions: Pain may have a detrimental effect on the course of mood disorders-the opposite holds. Promoting a timely recognition and management of such an often neglected comorbidity would therefore represent a primary goal toward the delivery of effective, multi-disciplinary care.

Abdominal Wall Endometriosis: Two Case Reports and Literature Review.

Background and objectives: Abdominal wall endometriosis, also known as scar endometriosis, is a rare condition that is becoming increasingly common. The recent rise in incidence is attributed primarily to the surge of cesarean births, figures that could be influenced in a positive manner considering the improvements brought towards the ultrasound diagnostic methods that have been made in recent years. Materials and Methods: Here we report the cases of two Caucasian women of 38- (G2P2) and 36-years old (G1P1), both subjected to an ultrasound examination due to a specific symptomatic panel reported during anamnesis. Independently of the current status, in the first patient, there were no reported symptom-specific associations with endometriosis, but she had a known history of mild hereditary thrombophilia; the second woman suffered from two conditions positively associated with endometriosis. Results: In both cases, abnormal structures were revealed, with the diagnostic(s) of endometriosis being histologically confirmed based on a set of features observed during the investigation. Conclusions: This paper aims to highlight the importance of reducing cesarean births and to consider the diagnosis of scar endometriosis in women with a history of obstetric or gynaecological surgeries who present with cyclic, recurrent abdominal pain.

Mini-Review on Lipofuscin and Aging: Focusing on The Molecular Interface, The Biological Recycling Mechanism, Oxidative Stress, and The Gut-Brain Axis Functionality.

Intra-lysosomal accumulation of the autofluorescent "residue" known as lipofuscin, which is found within postmitotic cells, remains controversial. Although it was considered a harmless hallmark of aging, its presence is detrimental as it continually accumulates. The latest evidence highlighted that lipofuscin strongly correlates with the excessive production of reactive oxygen species; however, despite this, lipofuscin cannot be removed by the biological recycling mechanisms. The antagonistic effects exerted at the DNA level culminate in a dysregulation of the cell cycle, by inducing a loss of the entire internal environment and abnormal gene(s) expression. Additionally, it appears that a crucial role in the production of reactive oxygen species can be attributed to gut microbiota, due to their ability to shape our behavior and neurodevelopment through their maintenance of the central nervous system.

Irritable Bowel Syndrome between Molecular Approach and Clinical Expertise-Searching for Gap Fillers in the Oxidative Stress Way of Thinking.

Irritable bowel syndrome (IBS) remains to date an intriguing functional gastrointestinal disorder. Recent studies described a multitude of exogenous factors that work together in IBS, gradually impairing intestinal lining cellular metabolism, including oxidative status balance, with or without a genetic background. Although the current biomarkers support the differentiation between IBS subtypes and other functional gastrointestinal disorder, they are mostly non-specific, referring to clinical, biochemical, and inflammatory imbalances. Since IBS could be also the result of deficient signaling pathways involving both gastrointestinal secretion and neuro-vegetative stimulation, IBS makes no exception from the oxidative hypothesis in the pathological mechanisms. Regarding the oxidative stress implication in IBS, the previous research efforts showed controversial results, with some animal models and patient studies reporting clear oxidative imbalance both on systemic and local levels, but still with no concrete evidence to point to a direct correlation between oxidative stress and IBS. Additionally, it seems that a major role could be also attributed to gut microbiota and their ability to shape our bodies and behaviors. Moreover, the genetic features study in IBS patients showed that several genetic similarities point to a possible correlation of IBS with affective spectrum disorders. Thus, we focus here the discussion on the assumption that IBS could in fact be more likely a stress-related disorder rather than a gastrointestinal one.

Systemic Oxidative Stress Markers in Cirrhotic Patients with Hepatic Encephalopathy: Possible Connections with Systemic Ammoniemia.

Background and objectives: Oxidative stress shows evidence of dysregulation in cirrhotic patients with hepatic encephalopathy (HE), although there are still controversies regarding the connections between oxidative stress and ammonia in these patients. The aim of this study was to evaluate the oxidative stress implication in overt HE pathogenesis of cirrhotic patients. Materials and Methods: We performed a prospective case-control study, which included 40 patients divided into two groups: group A consisted of 20 cirrhotic patients with HE and increased systemic ammoniemia, and group B consisted of 20 cirrhotic patients with HE and normal systemic ammoniemia. The control group consisted of 21 healthy subjects matched by age and sex. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) levels (lipid peroxidation marker), and ammoniemia were evaluated. Results: We found a significant decrease in SOD and GPx activity and also a significant increase of MDA levels in cirrhotic patients with HE as compared to the healthy age-matched control group (1.35 ± 0.08 vs. 0.90 ± 0.08 U/mL, p = 0.002; 0.093 ± 0.06 vs. 0.006 ± 0.008 U/mL, p = 0.001; and 35.94 ± 1.37 vs. 68.90 ± 5.68 nmols/mL, p = 0.0001, respectively). Additionally, we found significant correlations between the main oxidative stress markers and the levels of systemic ammonia (r = 0.452, p = 0.005). Patients from group A had a significant increase of MDA as compared with those from group B (76.93 ± 5.48 vs. 50.06 ± 5.60 nmols/mL, p = 0.019). Also, there was a compensatory increase in the activity of both antioxidant enzymes (SOD and GPx) in patients with increased systemic ammoniemia (group A), as compared to HE patients from group B. Conclusions: Our results demonstrated a significant decrease in antioxidants enzymes activities (SOD and GPx), as well as a significant increase in MDA concentrations, adding new data regarding the influence of oxidative stress in HE pathogenesis in cirrhotic patients.

A Narrative Review on Neuro-Ophthalmological Manifestations That May Occur during Pregnancy.

AIM: As a medical condition, pregnancy mandates the simultaneous treatment of both the mother and the fetus, making it a distinctive aspect of clinical medicine. MATERIAL AND METHOD: We analyze the physiological changes occurring in the eyes and brain during pregnancy, as well as the neuro-ophthalmological manifestations that can occur during pregnancy. Studies published in both English and other languages, case reports, and reviews from 2011 to 2023 onwards were included. All surveys were acquired by exploring the databases. RESULTS: We found a total of 2135 articles that showcase neuro-ophthalmic changes related to pregnancy: review and research articles (Science Direct 804, Web of Science 923, Scopus 345, and 63 Pub Med). In total, 86 studies were examined after applying the inclusion and exclusion criteria. Bilateral papilledema can be a warning sign for intracranial hypertension or cerebral venous sinus thrombosis. Additionally, when unilateral, it is important to differentially diagnose anterior ischemic optic neuropathy secondary to a hypercoagulant, compressive or inflammatory optic neuropathy, optic neuritis, or even orbital pseudotumor state. Severe eclampsia and preeclampsia can manifest as choroidal infarction, serous retinal detachment, and even cortical blindness. There can also be implications at the level of cranial nerves or transient Horner syndrome. CONCLUSIONS: Evaluating and treating a pregnant woman with neuro-ophthalmological manifestations is challenging. The obstetrician closely follows and has a medical relationship with the pregnant woman; hence he/she might be the first to be informed about the general condition of the pregnant woman or might request an ophthalmologic examination tailored to each specific case.

Vitamin B12 Ameliorates Pesticide-Induced Sociability Impairment in Zebrafish (Danio rerio): A Prospective Controlled Intervention Study.

Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component plays an important part in determining the overall picture. Moreover, the lack of therapies to relieve existing symptoms complicates the fight against this condition. As a result, animal models have been used to make biomedical research easier and more suited for disease investigations. The current study used zebrafish as an animal model to mimic a real-life scenario: acute exposure to an increased dose of pesticides, followed by prospective intervention-based therapy with vitamin B12 (vit. B12). It is known that vit. B12 is involved in brain function nerve tissue, and red blood cell formation. Aside from this, the role of vit. B12 in the redox processes is recognized for its help against free radicals. To investigate the effect of vit. B12, fish were divided into four different groups and exposed to a pesticide mixture (600 µg L-1 fipronil + 600 µg L-1 pyriproxyfen) and 0.24 µg L-1 vit. B12 for 14 days. The impact of the compounds was assessed daily with EthoVision XT 11.5 software for behavioral observations, especially for sociability, quantified by the social interaction test. In addition, at the end of the study, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured. The results showed significant improvements in locomotor activity parameters and a positive influence of the vitamin on sociability. Regarding the state of oxidative stress, high activity was found for SOD and GPx in the case of vit. B12, while fish exposed to the mixture of pesticides and vit. B12 had a lower level of MDA. In conclusion, the study provides new data about the effect of vit. B12 in zebrafish, highlighting the potential use of vitamin supplementation to maintain and support the function of the organism.

A Narrative Review Discussing the Efficiency of Personalized Dosing Algorithm of Follitropin Delta for Ovarian Stimulation and the Reproductive and Clinical Outcomes.

Background: Follitropin delta is the third recombinant human follicle-stimulating hormone (r-hFSH) expressed in a host cell line of human fetal retinal origin that currently emphasizes that the actual tendency of administration is a personalized dosing algorithm based on the anti-Müllerian hormone (AMH) and body mass index (BMI) for ovarian stimulation. Methods: In this context, we aimed, in the present manuscript, to gather all available data published between 2018-2022 regarding the co-administration and administration of follitropin delta and the clinical outcomes reported following an in vitro fertilization (IVF). Results: Follitropin delta is non-inferior in contrast to its previously launched agents for ovarian stimulation, enhancing a similar-to-superior response reflected by both the reproductive and pregnancy outcomes in parallel with a low risk of ovarian hyperstimulation syndrome (OHSS), being well tolerated. The body weight and AMH level are factors that may influence the outcome in a patient. Despite controversy and results that refute these arguments on several occasions, follitropin delta exceeds the benefits of conventional dosing with either follitropin alfa or follitropin beta. Thus, all post hoc, derived analyses and subsets of patients that participated in subsequent studies support this statement. Conclusions: Despite the relatively limited spectrum of data in the current literature, most authors brought potent proof, supporting the subsequent use of this drug depending on the patient's profile and overcoming ethnic-related limitations. Although others contradict these observations, this topic and drug possess substantial potential, which is why additional studies are mandatory to fill the existing gaps in our knowledge and expand these experiences at a larger scale supported by the obtained reproductive and clinical outcomes that clearly indicate an overcoming of all limitations.