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Background: Apolipoprotein E (ApoE) is a ubiquitous protein involved in maintaining cholesterol homeostasis and lipoprotein clearance from circulation. It is coded by three alleles (ε2, ε3, ε4) with six genotypes (ε3/ε3, ε3/ε4, ε2/ε3, ε4/ε4, ε2/ε4, and ε2/ε2). Several studies have shown a relationship between ApoE-specific isoforms and different diseases. There are few data about the prevalence of ApoE polymorphism in the Romanian population. We aimed to assess the prevalence of Apolipoprotein E alleles in a healthy population from Romania and compare it with the data found in other countries of Europe. Methods: ApoE genotype was examined in 187 unrelated healthy volunteers (131 males and 56 females) from the region of southwest Romania (mean age 48.04 ± 8.35 years). Analysis of ApoE genotype variants was done using the PCR method with allele-specific oligonucleotide primers. Results: The frequency of heterozygote genotypes ε2/ε3, ε2/ε4, and ε3/ε4 was 4.8%, 1.6%, and 24.73%, respectively, while the frequency of homozygote genotypes ε2/ε2, ε3/ε3, ε4/ε4 was 0.5%, 66.12%, and 2.1%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 6.9%, 96.25%, and 28.49%, respectively. East European countries have the lowest mean frequency of the ε4 allele (9.96%), and the highest frequency of the ε4 allele (23.38%) is in the Nordic Countries. Conclusions: The ε4 allele prevalence in this Romanian population is higher in comparison with other European countries, similar to Nordic countries of Europe.

This brief report sheds light on PDH cytopathy, a rare metabolic disorder associated with a variety of clinical symptoms and metabolic disturbances. The symptoms can range from mild to severe lactic acidosis and may also include neurological, cardiac, hepatological, and reproductive disorders. This disorder affects the metabolism of pyruvate and glucose in cells and causes a shift from the citric acid cycle to glycolysis. There are several potential metabolic steps that can be pathologically altered, and these often lead to the same outcome. The most common mutation demonstrates an X-linked semi-dominant inheritance. The symptoms are extremely diverse and the diagnosis is often difficult due to the complexity and heterogeneity of the disease. The gold standard for diagnosis remains the measurement of lactate levels in whole blood, both in the fasting state and after a sugar-rich meal. So far, there is no evidence-based treatment for PDH cytopathy. Therapeutic approaches such as thiamine and Q10 are often recommended, and a reduction in sugar and carbohydrate load in the diet can be helpful. In diabetic patients with PDH cytopathy, strict control of blood sugar levels can be beneficial, although this is often difficult to achieve., Received on April 18th, 2023 Peer review by Milad Medical Center completed on June 15th, 2023

With this short report we explore the intriguing association between hyperlactatemia, a common metabolic disturbance found in patients with mitochondrial disease, and narcolepsy-like symptoms. We delve into the biological mechanisms involved, the risk of misdiagnosing this as primary narcolepsy, and the unique challenges faced by patients suffering from both conditions.

H63D Syndrome is a genetic disorder characterized by iron accumulation in the body, which has been historically associated with hereditary hemochromatosis (HH). However, recent research has provided evidence that this syndrome, particularly type-1 H63D, has less in common with HH than with other metal accumulation diseases such as Wilson's Disease. This paper aims to elucidate the distinct features of H63D Syndrome, emphasizing the differences between H63D and HH, as well as the unique challenges associated with its treatment. Furthermore, we will explore the role of non-transferrin-bound iron (NTBI) in the pathophysiology of H63D Syndrome and its implications on cellular function and heart health.

After a long period of research, the International HFE H63D Research Consortium has now defined another clinical variant of H63D syndrome (henceforth referred to as H63D type-1) after evaluation of 1082 patient cases: "H63D syndrome type-2". Its characteristics and clinical picture are presented in this first preliminary paper on type-2 of H63D syndrome. &nbsp

Many researchers and clinicians still falsely and fervently claim that the HFE H63D gene does not play a clinically significant role. Because of this ignorance, patients die who could have been saved if their H63D syndrome had been diagnosed early. This ignorance is nothing less than a scandal.

The seductive temptation of ignorance: how micro-inflammation can cause serious diseases such as diabetes, obesity, heart problems or cancer-and yet be ignored because they are difficult to detect in the laboratory. Abstract Micro-inflammations are a phenomenon that has been attracting increasing attention from the scientific community in recent years. These small, persistent inflammatory responses that occur at a cellular level are thought to play a crucial role in the development and progression of many chronic diseases. Despite their importance, micro-inflammations are often ignored or overlooked in the clinical setting, and this can have serious consequences for patient health. In this paper, we will explore the mechanisms by which micro-inflammations occur, their impact on various health outcomes, and why it is dangerously wrong to ignore them. We will also discuss current approaches to managing micro-inflammations and the need for more comprehensive and targeted interventions to address this growing health concern.

In time, osteoarthritis (OA) generates the misalignment of the affected joint structures. However, due to the nature of bipedal gait, OA in the lower limb can also cause pathological gait patterns, which can generate instability and falls, with great consequence, especially in the aged population. With goniometry used to evaluate the range of motion (ROM) of joints, we wanted to evaluate how gender impacts gait dynamics in OA patients. For this study, we have compared 106 OA patients (74 females and 32 males) to age matched controls. All participants had their right leg as dominant. Video recording of normal gait was analyzed with a digital goniometry tool phone application, and the knee's ROM was measured in midstance and midswing moment of the gait. During midstance, significant extension and flexion of the knee excursion have been observed in both males and females. During midswing, knee OA presents more differences, whereas subjects with hip and knee OA present changes on the dominant knee. Midstance changes suggest that the knee's joint degenerative changes, such as synovitis, can be linked to hip OA secondary changes. Midswing changes in lower limb OA suggest a connection to the activities of daily life. Gender differences generated by OA must furthermore be studied in both lower limbs so that the best therapeutic approach can be chosen.

Since H63D syndrome was first described, the authors of this paper systematically investigated for the first time to what extent the adrenal glands, as an integral part of the HPA and SAM axes, are also affected by damage caused by non-transferrin bound iron (NTBI), a hallmark of H63D syndrome. Due to the rarity of the H63D syndrome, the representatives of a number of institutions that regularly deal with the topic in the context of their clinical and research activities have come together for this purpose. Thus, a small but significant amount of patient data could be collected worldwide, analyzed and evaluated, with surprisingly clear pathological results. A secondary aspect is that after reviewing the currently available literature, the team of authors came to the conclusion that the issue of HPA and SAM axes dysfunctions and adrenal synthesis activity seems to be also more frequent in other iron metabolic disorders than it is addressed to in everyday’s clinical practice. The result of this work is a warning call to closely monitor the catecholamine balance, the synthesis and control of all "stress hormones", the condition of the adrenal glands as well as other axis structures very early in the course of the H63D syndrome, in order to make unnecessary organ damages at least a little less likely, if not to prevent it to a large extent if detected early.

The evolution of rehabilitation treatments can be quantified through goniometric measurements. Thus, a video goniometer, and an app-based goniometry program can be both useful and a reliable method of obtaining a data base through which we can see if a certain rehabilitation treatment works out for our patients and during times such as the Covid-19 pandemic, a telemedicine approach can be done. Midstance is a sub-moment of the gait pattern, important in the stability of the lower limb, but that can also direct us towards a patient prone to falls. Osteoarthritis is a disease that causes high disability because of the cellular degradation that also affects normal gait. Four groups of subjects: subjects suffering from hip osteoarthritis, knee osteoarthritis, hip and knee osteoarthritis and control group, have been filmed and recorded their midstance joint range of motion in the Angles App. The dominant limb has been proven to have a more extended ankle in the hip osteoarthritis group, compared to knee osteoarthritis, hip and knee osteoarthritis or control group. Females have presented a more extended ankle, wearing high heels for a long period of time can be the cause of that. Subjects with knee osteoarthritis have presented a more flexed ankle in the dominant limb compared to the ones suffering from hip and knee osteoarthritis or control group. The ankle joint can also have its range of motion measured with a video goniometer, helping us compare results in between sessions of rehabilitation in osteoarthritic patients.

Osteoarthritis is one of the most debilitating diseases in Europe affecting the lower limb joints, especially the hip and knee, having a bad influence on gait in the long run as well. Rehabilitation physicians use gait in order for the whole body to be seen in ensemble, and through midstance as moment of gait to also take predilection to falls into consideration. Goniometry is the quantifiable measure of a rehabilitation treatment by measuring the range of motion of each treated joint and studied during time. The patients that volunteered to be part of this study have been divided into four groups, depending on the level of osteoarthritis present at the lower limb joints: hip, knee, both hip and knee osteoarthritis or control group with no osteoarthritis, have been asked to walk for a few times and the video recordings were uploaded into the Angles App where we measured the lower limb joint angles during midstance. Patients with knee osteoarthritis present a more extended hip on both dominant and non-dominant sides compared to the ones with hip osteoarthritis, hip and knee osteoarthritis or control group. The results can be explained through the body's kinematic chains that link the knee and hip, hip and pelvis during the midstance phase in the sagittal plane. A physician can use a video goniometry app in order for him to thoroughly evaluate an osteoarthritic patient as well as follow him or her during the entire course of treatment.

Few patients are fortunate enough to get detected in the early stages of tumors whether benignant or malignant. This chance, with multiple hidden ethical issues, has pitfalls for both doctors and patients. We are presenting two cases, a male and a female with diagnosis problems successfully managed even if they are not convinced about the necessity of the surgery. The male, aged 63 years, non-smoker, with occupational exposure for 41 years, oligosymptomatic, during a preoperative routine X-ray and thorax CT for a left hydrocele operated in June 2020, was identified an acidophilic tumor formation, located in the anterior mediastinum. Additional investigations revealed a left vocal cord paresis and the transthoracic needle biopsy raised suspicion of thymoma with glandular areas and clear cells, also confirmed by surgery, an N0 stage. In the second case, a 42 years female with a recent history of SARS-COV-2 viral infection, mild clinical form, while performing a CT scan to assess COVID status, discovered a tumor mass located in the anterior mediastinum. ENT examination establishes the diagnoses of subacute laryngitis, dysphonic syndrome under etiological observation, and chronic rhinitis. The excision of the mediastinal formation is performed with favorable postoperative evolution. Histopathological examination highlighted changes that argue the diagnosis of mature intrathymic teratoma. Apparently, there were fortunate cases with curative resection, but being oligosymptomatic also involved substantial efforts to convince the patient and the caregivers about the need for urgent surgery.

Testosterone is an important factor that influences the quality of life in men. The purpose of this study is to evaluate how testosterone level impacts the quality of life in patients with dilated cardiomyopathy.This cross-sectional single-center included 97 male patients with dilated cardiomyopathy, in whom serum testosterone was measured. Health-related quality of life was measured using the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). We used correlation and multivariable regression to assess the association between KCCQ-12 score, serum testosterone level, and clinical and paraclinical variables.The mean age of study participants was 58 (range 29-88). The mean LVEF was 25 ±8.61%. The average total serum testosterone level was 3.13 ±2.72 (range 0.19-13.5 ng/ml). The median global KCCQ-12 score was 44.8 (6.2-90.6) representing a poor to fair impairment in quality of life. There was an inverse correlation between the KCCQ-12 score and NYHA class (Pearson coefficient r = 0.847 p0.001) and a direct correlation with LVEF (r=0.445, p0.001). Also, the KCCQ-12 score correlated with hemoglobin level (r=0.214, p=0.037) and plasmatic creatinine level (r=-0.296 p= 0.004). In multivariable regression, the independent predictors of health-related quality of life were testosterone, LVEF, and NYHA class.The results of this study showed for the first time a significant direct relationship between serum testosterone levels and quality of life in patients with dilated cardiomyopathy.

H63D syndrome, now clinically known as Oslo syndrome (synonymous), is considered a very rare disorder that is difficult to recognize due to its multifaceted nature. Even with homozygous mutation of the HFE gene H63D and the simultaneous presence of the typical clinical symptoms, few clinicians dare to care for affected patients. This is inexplicable, because Oslo syndrome (H63D syndrome) looked at on the meta-level is nothing more than Wilson disease caused by NTBI iron., Peer review completed on May 2, 2023

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for plants, some bacteria, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, brain function, and steroid hormones. In the future, naturally organic B (NOB) species may become promising novel prebiotic candidates. We included the most relevant works about NOB species, starting from our 30-year research experience. NOB-containing compounds have been shown essential for the symbiosis between different kingdoms. New insights into the essentiality of NOB species for healthy symbiosis between the human/animal host and the microbiota will determine the use of natural B-based nutraceuticals to target the colon (colonic foods). The mechanism of action (MoA) of NOB species is related to both the B signaling molecule [autoinducer-2–borate (AI-2B)], as well as the fortification of the colonic mucous gel layer with NOB species from the specific prebiotic boron-rich diet. Therefore, both microbiota and the mucous gel layer of the colon become the NOB species’ target. This paper reviews the evidence supporting the essentiality of the NOB species on the symbiosis between the microbiota and the human/animal host with the stated aim of highlighting the MoA and target of these species.

Evidence-based medicine has shown for many years that homozygous mutations of the HFE gene H63D are by no means negligible. Not only can it cause, usually after a second hit, rather mild classical hemochromatosis, but it can also cause numerous other disorders of iron metabolism, such as hypotransferrinemia, changes in binding capacity, and others. In addition, it may lead - among other symptoms - to damages of the heart and the substantia nigra via a causal relationship that remains to be investigated, most likely via a cascade dysfunction in iron metabolism. The clinical facts are compelling. Any physician who dismisses mutations of the HFE gene H63D as clinically irrelevant risks the health and life of his patient. We report two patients with an HFE H63D mutation who were treated almost two decades too late because of outdated expertise., Peer review completed, August 12th, 2022. Responsible: Team III (Dr. Kramer) of Swabian Research & Publishing (www.swabian.org)

Die Triglyceride stehen im klinischen Alltag nach wie vor im Schattes des Cholesterins. Zu Hypertriglyceridämie befinden sich zu wenig solide Daten, teils sogar überkommende im Umlauf. Anlass für ein Whitepaper zum Thema zu erstellen, das auf soliden (i.S.v. unabhängigen) Studien und der Erfahrung in der tagtäglichen Behandlung von Patienten am beruht. Dabei hat die Studiengruppe all jene Paper nicht mit aufgenommen, welche sich nicht mit der praktischen alltäglichen Erfahrung decken. Zur Kenntnis genommen wurden diese jedoch selbstverständlich auch. Die Wahl der Sprache, Deutsch, war ein Wunsch des Kollegen Adrian Tudor, der gerade im deutschsprachigen Raum Defizite in der Versorgung von Patienten mit Hypertriglyceridämie sieht und in seiner Zeit als Klinikarzt in einem deutschsprachigen Land entsprechende Erfahrungen gemacht hat. Selbstverständlich wurde aber auch die englischsprachige Literatur gründlich gesichtet. Als evidenzbasiert stufen wir die folgenden Aussagen ein: Hypertriglyceridämie ist mit einem erhöhten Risiko für Herz-Kreislauf-Erkrankungen wie Herzinfarkt und Schlaganfall verbunden, chronische Hypertriglyceridämien können Arteriosklerose und eine nicht-alkoholischer Fettleber veryrsachen, Mangelernährung in Kliniken und Heimen sowie alle Formen der Magersucht können sind der häufigste Grund für zu niedrige Triglyceridwerte, was nicht etwa gesund sondern schädlich ist

Skin cancer, especially malignant melanoma, can vary greatly in appearance and usually develops very quickly. Therefore, the ABCDE rule (also known as the ABCD rule in some countries) was propagated many years ago to help medical laymen to recognize for themselves when it is time to see a dermatologist. But how effective is this rule? Our previous work clearly demonstrates that another self-monitoring protocol has a higher sensitivity and better results than the outdated ABCDE rule: the C-Rapid-H-Plus Protocol. Based on this, a simple algorithm was developed which appeared to give quite promising results. Now we can present a completely new algorithm that has proven to be more reliable than dermatoscopy in predicting the need for excisional biopsy in a collective of 421 patients. The CRHP Advanced Risk Calculator, also based on the C-Rapid-H-Plus protocol, is of great value for both, in-person and telemedicine settings.

Excision calculator based on the C-Rapid-H-Plus Protocol (for physicians only)

During the development of a vaccine to protect against the Sars-CoV-2 virus, it became apparent that one vaccine in development (Australia) lead to false positive results in the usual tests for HIV1/2 antibodies. The project was subsequently swiftly terminated and the topic disappeared from the attention of science and the media. Howeber, thanks to access to anonymized patient data through our international network, whistleblowers and case reports within our own reporting system for unusual events, we have come to the hypothesis that this "Australian effect" can also occur with other Sars-CoV-2 vaccines, albeit to a much lesser extent. In individual cases, however, this can have dramatic consequences. For this reason, we are publishing a hypothesis, contrary to our usual conventions. In no way do we wish to minimize the willingness to get vaccinated, nor do we wish to reproach any pharmaceutical company. Nevertheless, it is important to present the facts as they appear to us for discussion and to avoid adverse consequences should such an effect actually materialize in individual cases., Peer review process successfully completed on Dec 13, 2022 (www.swabian.org)

Chris Wymant and an entire armada of scientists published a small paper titled "A highly virulent variant of HIV-1 circulating in the Netherlands." The general media have picked up on this and are giving the impression that HIV is now a more dangerous infection. This is not the fault of the Wymant and colleagues, but it is highly problematic. This more than 30 years old knowledge, which is now published with big headlines outside the medical press as lurid news, is likely to provoke misunderstandings in the general population. A renewed ostracism and stigmatization of the usual risk groups is now a real prospect. The findings presented in the aforementioned paper should have been addressed exclusively to health professionals and should have better never ended up in the hands of commercial media.

For many patients with severe Covid-19 disease of the pre-Omicron era, recovery is far from over with the end of acute symptoms. The authors of this paper have reviewed the currently available studies and conclude that Long-Covid appears to be a serious, sometimes even life-threatening syndrome. However, it seems to have good prospects for full recovery with multidisciplinary and evidence-based post-treatment care, which is, however, still lacking in Europe and North America. The Omicron variant appears to be a game changer in this regard as well. So far it seems that Long Covid is no common consequence of Sars-2-Omicron Disease.

The emergence of the Sars-CoV-2 Omicron variant(s) was a tipping point which led from the 2020/2021 Covid-19 pandemic to a surprisingly early endemic situation. Contrary to what is discussed by some virologists, a replacement of Sars-CoV-2 Omicron by another variant that produces more clinically problematic courses is only a theoretical possibility. In real life this will not happen. Instead Omicron seems to be even less lethal than the endemic hCoVs we have been knowing for decades. Therefore, now is the time to develop entirely new vaccines, not only against the Sars-CoV-2 virus but also to protect vulnerable populations against the human coronaviruses OC43, HKU1, 229E, and NL63. These coronaviruses are, as of early 2022, a greater public health threat than the Sars-CoV-2 virus with its Omicron variants.

According to our assessment, the Sars-CoV-2 pandemic has already reached an endemic stage and the pandemic has ended. This white paper published by our small research group briefly documents the situation at the end of January 2022, without claiming to be exhaustive.

In the wake of the Sars-CoV-2 pandemic, some scientists and pharmaceutical companies have come to the unsettling conclusion that the Covid-19 pandemic can only be overcome by vaccination and the constant administration of booster vaccines, at a frequency more akin to the effect of a depot injection than a vaccination. As much as we welcome and recommend all licensed vaccinations (including the rather new mRNA and vector products), we strongly support the critical rejection by EMA of the temptation to keep administering boosters at ultra-short intervals. Vaccines are by definition not regular drugs and have not been authorized as such.

Aquaporin-4 (AQP4) is located mainly in the astrocytic end-feet around cerebral blood vessels and regulates ion and water homeostasis in the brain. While deletion of AQP4 is shown to reduce amyloid-β (Aβ) clearance and exacerbate Aβ peptide accumulation in plaques and vessels of Alzheimer’s disease mouse models, the mechanism and clearing pathways involved are debated. Here, we investigated how inhibiting the function of AQP4 in healthy male C57BL/6 J mice impacts clearance of Aβ40, the more soluble Aβ isoform. Using two-photon in vivo imaging and visualizing vessels with Sulfurodamine 101 (SR101), we first showed that Aβ40 injected as a ≤ 0.5-μl volume in the cerebral cortex diffused rapidly in parenchyma and accumulated around blood vessels. In animals treated with the AQP4 inhibitor TGN-020, the perivascular Aβ40 accumulation was significantly (P

Even without symptoms, many people are at risk of transmitting the SARS-CoV-2 virus. This is pointed out by researchers from Beijing University based on a meta-analysis by QiuyueMa et al. and has never been more important due to the rise of Sars-CoV-2 Omicron.It is the first time since the pandemic began with isolated cases in early fall of 2019 in the city of Wuhan (CCP-China) that public health authorities lose control entirely over the development of the pandemic without any tool to counteract this unfolding event. Sars-CoV-2-Omicron is unstoppable. &nbsp

The most dangerous and aggressive skin cancer, malignant melanoma, can have a wide variety of appearances and usually develops rapidly. The ABCDE rule (also known as the ABCD rule in some countries) has therefore been promoted to help lay people recognize when it is time to see a dermatologist. But how effective is this rule? Our data clearly shows that another self-monitoring protocol has a superior sensitivity and better outcomes than the outdated ABCDE rule: theC-Rapid-H-Plus Protocol.