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In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin's ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.

Introduction: The proliferation of literature regarding the COVID-19 pandemic has served to highlight a wide spectrum of disease manifestations and complications, such as thrombotic microangiopathies. Our review with a brief case presentation highlights the increasing recognition of TTP in COVID-19 and describes its salient characteristics. Methods: We screened the available literature in PubMed, EMBASE, and Cochrane databases from inception until April 2022 of articles mentioning COVID-19-associated TTP in English language. Results: From 404 records, we included 8 articles mentioning data of 11 patients in our review. TTP was predominantly reported in females (72%) with a mean age of 48.2 years (SD 15.1). Dyspnea was the most common symptom in one third of patients (36.6%). Neurological symptoms were reported in 27.3% of cases. The time to diagnosis of TTP was 10 days (SD 5.8) from onset of COVID-19. All 11 cases underwent plasma exchange (PLEX), with a mean of 12 sessions per patient, whereas 6 cases received Rituximab (54.5%), and 3 received Caplacizumab (27.3%). One patient died from the illness. Conclusion: This review of available literature highlights the atypical and refractory nature of COVID-19-associated TTP. It required longer sessions of PLEX, with half of the patients receiving at least one immunosuppressant.

Adult X-linked hypophosphatemia (XLH) patients present with specific symptoms, including enthesopathies (e.g., ossification of longitudinal ligaments (OPLL), osteophytes around large joints, and enthesopathy in the Achilles tendons), early osteoarthritis, the development of severe secondary and tertiary hyperparathyroidism (SHPT/THPT), and the subsequent progression of chronic kidney disease (CKD). In addition, these patients exhibit the typical phenotypes of osteomalacia, such as pseudofracture and fracture in weight-bearing bones, odontitis, and tooth abscesses. The mechanism underlying enthesopathy development is unknown; however, a common underlying mechanism among XLH and autosomal recessive hypophosphatemic rickets (ARHR1/2) due to mutations in PHEX, DMP1, and ENPP1 is assumed. Clarification of the pathogenesis and drug discovery for this complication is an urgent issue, as many adult XLH patients suffer subsequent debilitating nervous symptoms or impingement syndrome, and existing treatments are ineffective. Severe SHPT and THPT are associated with conventional therapy, including active vitamin D and phosphate supplementation, and complicated and careful adjustment of dosages by experienced clinicians is required to avoid SHPT/THPT. Burosumab is a very effective therapy without risk for the development of SHPT/THPT. However, indications for this drug should be carefully considered, along with cost-effectiveness, guidelines or recommendations, and the health care system of each country.

The scientific, private, and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike protein the only vaccine target or is a vaccine cocktail better?

Purpose The main purpose of this study was to investigate the effects of 12 months of rhPTH (1–84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1–84) [rhPTH (1–84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. Methods It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations. Results Fourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1–84) for 12 months. At 12 months of rhPTH (1–84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1–84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described. Conclusions Biochemical and clinical results confirm the efficacy and safety of rhPTH (1–84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

Background: Bibliometric analysis provides insight into knowledge gaps of a specific field. We want to know what part of medical care has been the subject of research in a group of Mexican physicians. The Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) cares for a wide spectrum of disease and it provides a unique vision of what specialists has investigated about health. Methods: Papers belonging to “ISSSTE” affiliation were harvested and downloaded to .csv Excel files from the Scopus database including most bibliometric variables. VOSviewer, biblioshiny and bibliometric were used to conduct the bibliometric. Results: 2,063 papers were found and re-trieved; internal medicine had the greatest number of papers with 831; nine institutions were listed claiming “ISSSTE” as their mother affiliation; original papers represent 82% of the total and 52% of them were written in Spanish. Research production in Mexico City and the most productive center is Centro Médico Nacional 20 de Noviembre. Discussion: We identified main institutions, prolific authors, top-cited researchers and their affiliations, however, our paper is a call to action for the medical community in Latin America to join our efforts in building a solid group of researchers for the future of science.

Tungiasis has been included in the WHO list of Neglected Tropical Diseases, but systematic data on the occurrence are scarce. We analyzed data on the occurrence of tungiasis in the 184 munici-palities of Ceará State in Northeast Brazil, based on an online open rapid assessment question-naire focused on health professionals and other key stakeholders. Questions included the occur-rence of tungiasis, severe cases, cases in animals and seasonal variations of the disease. There were in total 1,265 individual data entries available (1 to 104 per municipality) from all munici-palities of the state. A total of 181 (98.3%) of municipalities reported the occurrence of tungiasis in the past or currently, 120 (65.2%) reported current occurrence, 155 (84.2%) severe cases in the past or currently; and 47 (25.5%) reported severe cases currently. A total of 132 (71.7%) municipalities reported tungiasis in animals, most commonly in dogs (97), pigs (80), cats (50), horses (20), cattle (8) and goats (6). Most municipalities mentioned the seasonality of tungiasis (n=146; 79.3%). There was no report of any specific tungiasis control program. Our data show that tungiasis and severe tungiasis commonly occur in Ceará state and that tungiasis is a significant public health issue for both humans and animals. An integrated One Health approach is needed to reduce dis-ease burden, including human and animal health, and the environment.

Prevalence of malnutrition among children under five is alarmingly high in Pakistan. However, there are ready-to-use therapeutic foods (RUTF) available which may be used to treat children with severe acute malnutrition (SAM). This study aims to assess the efficacy of prebiotics as a synergistic additive to RUTF to enhance blood parameters and anthropometric measurements in children with uncomplicated SAM living in Southern Punjab, Pakistan. A double-blind parallel treatment randomized controlled trial was conducted on 204 children aged between 6-59 months. Participants were randomized and allocated to the placebo (n=102) and experimental arms (n=102) at a 1:1 ratio. One group of children were provided RUTF and 4 g prebiotics, while the other group were given RUTF and starch as a placebo. Participants recruited for both arms were given treatment for eight weeks, and then their biochemical and anthropometric outcomes were evaluated. A substantial difference between the mean weight, mid upper arm circumference, haemoglobin, haematocrit, platelet count, mean corpuscular volume, mean corpuscular haemoglobin, and albumin was revealed. Conclusively, supplementation with RUTF and prebiotics has proven to be an efficient, effective and safe therapy for children suffering from SAM to improve their growth and development indicators and reduce the dangers of malnutrition in comparison to RUTF alone.

Metabolic surgery can promote integrated physiologic improvement to ameliorate metabolic illness, particularly type 2 diabetes. Nevertheless, the therapeutic scope has been limited by unexpectedly inconsistent surgical outcomes. Therefore, the purpose of this study is to overcome the obstacles by determining the core mechanism of conflicting results. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified types of duodenal-jejunal bypass procedures, were compared to comprehend specific surgical patterns from distinctive perspectives. Patients in exclusively nonobese groups are subjected to avoid compounding by weight fluctuations. During intestinal anastomosis, the epithelial identity of the succeeding intestine is replaced by that of the proximal epithelium through altered crosstalk between the epithelium and opposing mesenchymal cells. The rapid turnover rate and compensatory proliferation of the succeeding intestine accelerate the propagation of the replaced epithelium. Propagation of replaced epithelium could provoke inconsistent outcomes of metabolic surgery. The major determinants of the conflicting results of metabolic surgery are inadequate duodenal exclusion and inappropriate length of the biliopancreatic limbs. The replaced enteroendocrine cells during regeneration provoke inconsistent outcomes of metabolic surgery. The critical factors are the type and density of enteroendocrine cells distributed at the terminal end of the preceding proximal intestine.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin to some extent underlies all other categories of age-related damage as defined by Dr. Aubrey de Grey. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. It may suffice for the next few hundred years by itself. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss ways of removing it from post-mitotic cells (and then the body).

Relapsed acute lymphoblastic leukemia (ALL) represents a continuous challenge for the clinician. Despite recent advances in treatment, the risk of relapse remains significant. The clinical, biological, cytogenetic, and molecular characteristics may be different at the time of relapse. Current comprehensive genome sequencing studies suggest that most relapsed patients, especially those with late relapses, acquire new genetic abnormalities, usually within a minor clone that emerges after ALL diagnosis. We report the case of a 23-year-old young woman diagnosed with Philadelphia chromosome negative B-cell acute lymphoblastic leukemia. The patient underwent allogeneic stem cell transplantation (allo-HSCT) after complete remission. Although having favorable prognostic factors at diagnosis, the disease relapsed early after allo-HSCT. The cytogenetic and molecular exam at relapse was positive for the Philadelphia chromosome, respectively for the bcr-abl transcript. What exactly led to the relapse of this disease in a more aggressive cytogenetic and molecular form, although there were no predictive elements in the diagnosis of this relapse?

(1) Background: This paper investigates the epidemiological risk related to temperature before and during COVID-19 in Italy; (2) Methods: Deaths in 2015-2019 and temperatures were correlated. Excess and COVID-19 deaths were examined to estimate the relationships with temperatures; (3) Results: Annual deaths were higher during the cold months (+45,000, SD = 4,700, S = 21). The scenario worsened during COVID-19. Mortality was higher during minimum temperature periods, although the curve moderately rose in the warmest months (r = -0.75, 95% CI = [-0.87; -0.56], S = 23). COVID-19 deaths showed a decreasing seasonality. Monthly excess deaths during COVID-19 were high (+4,200, IQR = [2,800; 8,000], S = 28) with a doubt of seasonality. COVID-19 mortality was correlated with regional latitude (r = 0.86, 95% CI = [0.68; 0.94], S = 20). Discrepancies between COVID-19 and excess deaths were found. The exposed population was subject to aging; (4) Conclusions: The epidemiological risk in Italy is seasonal and geographically dependent. Low and very high temperatures can lead to mortality peaks. Therefore, COVID-19 and any other epidemiological risk must be evaluated in light of this evidence. Health systems need to be strengthened during cold and extremely hot periods. Future research should investigate these phenomena at the causal level.

Background. The main impetus behind the worldwide Covid-19 vaccination campaign in 2021 was to reduce the mortality attributed to SARS-CoV-2 infection in the preceding year. Nevertheless, rigorous analyses of the mortality benefits conferred by this massive vaccination effort have been lacking. Methods Statistics offers us an essential methodological approach for measuring the impacts of Covid-19 vaccination on public health. The mathematical relation between vaccinated-alive groups can be repeated between vaccinated-dead groups with relatively high statistical reliability because of the large population numbers involved. This method also confers greater statistical usefulness because it eliminates the Simpson effect. Results Calculations were performed for each of the following five(5) four-week intervals: weeks 35-38 (2021), weeks 39-42 (2021), weeks 43-46 (2021), weeks 47-50 (2021), and weeks 51(2021)-2(2022). The results obtained confirm that the mortality of the vaccinated coronavirus-infected groups was 14.5% higher on average than the mortality of non-vaccinated coronavirus-infected groups. Conclusions Vaccinated infected groups appear to have higher average mortality than their non-vaccinated infected counterparts. The findings suggest the legitimacy of extending the statistics between vaccinated living and vaccinated dead individuals for different age groups. Calculating the impact of Covid-19 vaccination on the mortality rate is a necessary step towards satisfying the first principle of medicine: “Primum non nocere”, “Do no harm”.

Innovation development in healthcare has paved the path towards the improvement in system efficiency, patient care and cost-effective healthcare services, increasing the overall efficiency of the healthcare system in a significant manner. Electronic medical record system has fostered interoperability and collaboration in healthcare departments by enabling different systems to exchange and use patient data. This trend has been accelerated dominantly by the pandemic, leading to increased use of telemedicine, referring specifically to the use of electronic communication to provide healthcare services remotely. Moreover, an increased prevalence towards the use of artificial intelligence and machine learning in healthcare has contributed effectively towards the rigorous and informed analysis of large amounts of data as well as to identify patterns or trends that may be useful for improving care delivery or identifying potential issues. A unified electronic medical record System that will generate competitive opportunities and success prospects with reference to enhanced interoperability in US healthcare departments, can contribute towards the improvement in the quality and efficiency of care by making it easier for healthcare providers to access and share patient information as well as reducing the risk of errors in effective patient care.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. However, due to organ shortages, this treatment can only be applied to carefully selected patients according to clinical guidelines. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging, like radiology. With the help of these technologies, laborious tasks can be automated, and new lesion imaging criteria can be developed based on pixel-level analysis. Our objectives are to review the developing AI applications that could be implemented to better stratify liver transplant candidates. The papers analysed applied AI for liver segmentation, evaluation of steatosis, sarcopenia assessment, lesion detection, segmentation, and characterization. A liver transplant is an optimal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease. Furthermore, AI could provide solutions for improving the management of liver transplant candidates to improve survival.

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

Background: Free-living amoebas (FLA), also amebas, are eukaryotic and mitochondrial microorganisms that are capable of growing in any environment, aquatic or terrestrial. These free-living amoebas are mostly non-pathogenic to humans. However, there exist some highly pathogenic species, such as Acanthamoeba — mainly T-4 genotype —, Naegleria fowleri (known as brain-eating amoeba), and Balamuthia mandrillaris. They can be called "brain-eating amoebas” because of their ability to cause substantial destruction of brain tissue. There is no standard treatment; immunological processes which predispose humans to acquire and infection and, then, a disease are unknown. In addition, there are other species of free-living amoebas such as, Sappinea pedata, Vermamoeba vermiformes, Vanellas sp,Vahlkampfia sp., and, more recently, Paravahlkampfia francinae, which is less virulent and aggressive than the first three mentioned above. Methods: All CSF samples were evaluated in our laboratory under the microscope. Monoxenic and axenic cultures were negative as well as the presence of cysts or exponential growth. PCR was negative using the FLA primers. Results: Under close observation of sterile CSF, we can see mobile forms of non-human cells. None of the observed forms has the morphotype of Acanthamoeba, Naegleria sp. or Balamuthia mandrillaris. Conclusions: Due to these findings, we know these structures can be observed in the CSF and many of them do not form cysts as others do. In addition, these microorganisms are uncultivable in conventional medium culture to FLA and impossible to detect even when using molecular tools such as PCR, using the primers for EUK A/B or 18s RNAr gene as a target.

Preventive behavior is one of the main strategies to contain the spread of the coronavirus, understand the factors that influence adherence or hesitation to protective measures and the way the population behaves during a health crisis is of great importance. Aim: To analyze the factors associated with adherence to protection measures against Covid-19 in Brazil. Method: cross-sectional study, survey type online, between the period of August 2020 and February 2021. The population included in the study were Brazilians, aged 18 years or older. Non-probabilistic sampling was used to obtain the sample. The data was stored on the "Redcap" platform and analyzed in a descriptive and inferential approach. Results: The sample consisted of 1,516 people, women adopted 10% more protective measures than men, people with higher education level and higher income, within the age group between 40-59 years, were those who most adhered to the measures imposed by health agencies. Carrier of Asthma, Diabetes Mellitus, Systemic Arterial Hypertension, Obesity and smoking were factors that increased the adherence of protective measures in the fight against COVID-19. Conclusion: Being female, aged between 40 and 59 years, higher education, smoking, not having a religion, having health insurance, and being a carrier of chronic diseases were associated with greater adherence to protective measures against COVID-19.

Today, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires comprehensively address the adversities of vulnerable subgroups, specifically refugee children. This review's objectives are to (1) identify current ACE questionnaires and determine if they are suitable for assessing refugee children’s adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children’s experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children's adversities to understand how their well-being is affected and to identify children at risk.

COVID-19 pandemic-related pressures on primary care may have driven inappropriate continuation of antibiotic prescriptions. Yet prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. Using the OpenSAFELY-TPP analytics platform, we analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between Jan 2020–2022. In-depth analysis was conducted on Jan 2020 (“pre-pandemic”) and Jan 2021 (“pandemic”) cohorts. Per-patient prescribing and clinical conditions were determined by searching primary care record data using clinical code lists. Repeat prescribing was defined as >=3 prescriptions in a 6 month lookback period. Associations between demographics (e.g. age, sex, geography) and repeat/non-repeat prescribing were explored using unadjusted risk ratios. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines -26% vs -11%, respectively). In the pandemic cohort, older patients were at higher risk of prescribing (especially repeat prescribing). The most common clinical conditions for repeat prescribing were COPD comorbidity and urinary tract infection. Comorbidities were more common among repeat vs non-repeat prescribed patients. In the pandemic cohort, vs pre-pandemic, repeat and non-repeat prescribing for comorbidities generally declined less compared with shorter-term conditions (infections, including COPD exacerbation/lower respiratory tract infection). Our findings inform ongoing development of stewardship interventions in England..

Sand-cement bound screed floor layers are at risk for work-related low back pain, lumbosacral radicular syndrome and knee osteoarthritis given their working technique of level-ling screed with their trunk bended and mainly supported by their hands and knees. To reduce the exposure of the physical demands of bending of the trunk and kneeling, a manually moved screed levelling machine was developed for floor layers in the Netherlands. The aim of this pa-per is to estimate the potential health gain of the manually moved screed levelling machine on the risk of low back pain (LBP), lumbosacral radicular syndrome (LRS) and knee osteoarthritis (KOA) compared to the traditional working technique. The potential health gain was assessed using the epidemiological population estimates of the Population Attributable Fraction (PAF) and the Potential Impact Fraction (PIF) combined with work-related risk estimates for these three disorders from systematic reviews. The percentage of workers exceeding these risk esti-mates was based on worksite observations among in total 28 floor layers. For LBP, 16/18 work-ers were at risk using the traditional working technique with PAF=38%, and for the manually moved screed levelling machine this was 6/10 with PIF=13%. For LRS, these data were 16/18 with PAF=55% and 14/18 with PIF=18% and for KOA, 8/10 with PAF=35% and 2/10 with PIF=26%. A manually moved screed levelling machine might have a significant impact on the prevention of LBP, LRS and KOA among floor layers in the Netherlands and a health impact assessment is a feasible approach to assess health gains in an efficient way.

Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent outbreak in several countries around the world. A 39-year-old male with HIV-HBV coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox infection, presented to our hospital with disseminated dermatosis (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for Mpox. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. After 65 days of Mpox PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox infection because it could be related to higher mortality.

Objectives: Hemoglobin A1c (HbA1c) levels play an important role in the diagnosis, screening, and monitoring of treatment in diabetes. The aim of our study is to determine whether there is a relationship between HbA1c levels and age and gender in Turkish adults who have not been diagnosed with diabetes.Materials and Methods: This retrospective study included 6776 Turkish adults without diabetes. Cross-sectional analyzes of A1C levels were performed between different age and gender categories. In statistical analysis, t-test, linear regression analysis, one-way ANOVA analysis, and LSD post hoc were used.Results: HbA1c levels in the individuals examined by dividing into different age groups increased with age in all groups. In our study, HbA1c levels were significantly higher in males than females (p < 0.001) in all groups, especially between the ages of 30-49, and were positively associated with age for males and females. There was a positive correlation between HbA1c and age in both men and women aged 30-49 years (P < 0.05). In the HbA1c ≥ 6.5 group, HbA1c levels gradually decreased with age in both genders, and no significant effect of age on Hb1Ac level was detected (p > 0.05). Conclusion: Our results showed that it is important to evaluate the effects of age and gender when using HbA1c levels in the diagnosis, screening, and treatment of diabetes, especially in the young and middle-aged population. Applying this situation to daily practice may reduce the misdiagnosis of diabetes in elderly patients, overtreatment of diabetes, and its associated risks.K

Background: Chronic kidney disease (CKD) is a common complication of non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD), increased serum creatinine ≥50%, renal replacement therapy (RRT), and death in pre-transplant, peri-transplant and post-transplant period. Results: 74 patients were studied (7 heart transplant, 34 liver transplants, and 33 lung transplant). Patients who were not followed-up by nephrology in the pre-transplant (p

Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency, to evaluate the diagnostic performance of serum ferritin in polycythemia vera and to describe the mechanisms of this association. This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis. Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR=115; 95% CI [14.4-918.2], p

Despite being under development for decades, RNA therapeutics have only recently emerged as viable platform technologies. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.

Gout is not only associated with obstructive sleep apnea (OSA), but the intermittent episodes of hypoxia that occur with OSA may also have a role in causing gout. Epidemiological studies have documented a higher incidence and prevalence of gout in individuals diagnosed with OSA than in individuals never diagnosed with OSA. The pathophysiology of OSA’s chronic episodes of hypoxia leading to hyperuricemia and gout involves boththe overproduction and underexcretion of uric acid. Treating OSA may be an additional way to control gout and its life-threatening comorbidities. Clinicians are urged to evaluate their patients with hyperuricemia/gout for OSA as it may lead to alternative ways to control gout with superior outcomes that simply pharmacologic treatment alone.

Objective: To investigate the feasibility and preliminary effects of a 12-week home-based moderate intensity cycling programme in stroke survivors. Design: Single-blinded, parallel group, Randomised Controlled Trial Setting: Home-based Participants: Participants will be survivors of first-ever stroke and randomly assigned to an Active Cycling Group (ACG) or control group. Intervention: The ACG performed a 12-week home-based cycling programme, three sessions per week. Work intervals were executed at 75% of the maximal heart rate (HRmax), recovery intervals at 50% of HRmax. Work interval duration increased from three ten-minute intervals to 30 minutes continuous cycling. The control group completed a 12-week neurocognitive exercise programme. Main outcome measurements: Primary outcome measures are compliance with training, adherence to protocol and safety as measured by adverse events. Secondary outcome measurements included a: simplified modified Rankin Scale questionnaire (stroke severity), Six-Minute Walking Test (walking ability), Ten-meter Walk Test (walking ability), Rivermead Mobility Index (walking ability), graded submaximal cycling test (exercise capacity), Physical Activity for Individuals with Physical Disability questionnaire (physical activity), EQ-5D-5L (quality of life), Stroke Specific Quality of Life questionnaire (quality of life), Montreal Cognitive Assessment (cognition), General Self-Efficacy Scale (self-efficacy), and Exercise Self-Regulation Questionnaire (self-regulation).

Introduction: CT perfusion (CTP) is an alternative tool to assess cerebral hemodynamics in brain trauma. As traumatic acute subdural hematomas (ASH) are severe lesions commonly associated with poor outcome, we aimed to evaluate the brain hemodynamics in this population. Methods: Five patients admitted at the emergency department sustaining traumatic acute subdural hematoma were evaluated. Preoperative CTP was performed immediately after nonenhanced head CT scan. Postoperative CTP was performed in four patients. The outcome was assessed 6 months after surgery using the extended Glasgow Outcome Scale. Results: 4 male and 1 female were evaluated. Mean age was 46y (SD: 8.1). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). The main mechanism of trauma was falling (four patients). There was a general improvement in cerebral blood flow (CBF) after surgery from 23.9 (SD: 6.1) to 30.7 ml/100g/min, (SD: 5.1) and in mean transit time (MTT) from 7.3 (SD: 1.3) to 5.8s (SD:1.0), although it is not statistically significant (p=0.06 and p=0.06, respectively). There was still a reduction in the cerebral blood volume (CBV) media when compared to the value after surgery, from 2.63 (SD: 1.10) to 2.34 ml/100g (SD: 0.67), which is not statistically significant (p=0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome was 0.94 (p=0.054). Only one patient died (three days after surgery). This patient was victim of car crash and had the highest preoperative MTT (9.97 seconds) and CBV (4.51 ml/100 g). Conclusion: Post-operative improvement of hemodynamic CTP parameters may be correlated with outcomes after ASH. Further studies with larger samples are required to confirm this hypothesis.

Introduction: Levosimendan is a positive inotropic molecule that does not reduce splanchnic circulation and has anti ischemic properties by opening mito KATP channels. Cirrhosis is a chronic and diffuse process characterized by fibrosis and the conversion of typical liver architecture into structurally abnormal nodules. In the late stages of the disease, cirrhosis is responsible for organ failure and complications such as cirrhotic cardiomyopathy and hepatic encephalopathy. Material and methods: We examined the effect of levosimendan in rat models of liver cirrhosis. Male Wistar rats were divided into four groups: Group A: cirrhotic rats 14 days after bile duct ligation (BDL); Group B: control (intact rats); Group A1: BDL and levosimendan (liver cirrhosis induced by bile duct ligation plus intraperitoneal administration of levosimendan); Group B1: control and levosimendan (intact animals with normal liver function treated with an intraperitoneal injection of levosimendan). Each group was subjected to blood sampling to determine GOT, GPT, and bilirubin at baseline, two weeks after surgery, and four days after treatment. In addition, echocardiography was performed in all the groups simultaneously. At the end of the experiments, the rats were subjected to cerebral and hepatic microdialysis and sacrificed. Results: Serum GOT, GPT, and bilirubin in Group A1 (GOT 304 UI/L, GPT 60 UI/L, BIL 3,9 mg/dl) were considerably lower than in Group A (GOT 320 UI/L, GPT 67,16 UI/L, BIL 6,4 mg/dl). The Ejection fraction value decreased significantly postoperatively in Group A (preop 55,66%, BDL 38,85%) and was highest after treatment with levosimendan (Group A1 48,38%). Significant histological differences were detected between the experimental groups (Group A Sheuer staging 3, severe fibrosis, Group A1 Sheuer staging 0-2 no, mild and moderate fibrosis). Group A had a higher value of Lactate, Pyruvate, Glycerol, and Glutamate cerebral microdialysate concentrations (Lac 0.37mM, Pyr 16.25 mcM, Glyc 15.72 mcM, Glut 15.8 mcM) in comparison with BDL rats treated with levosimendan (Group A1 - Lac 0.31 mM, Pyr 6.3 mcM, Glyc 13.66 mcM, Glut 11.15 mcM). Glucose concentrations in cerebral dialysate from Group A were significantly lower (0.13 mM) than in Group A1 (0.25 mM). Glucose and Glycerol concentrations in liver microdialysate from Group A were significantly lower (Gluc 0.95 mM, Glyc 1 mcM) than in Group A1 (Gluc 1.6 mM, Glyc 3.4 mcM). Conversely, in liver dialysate from Group A (0.52 mM), lactate was significantly higher than in Group A1 (0.35 mM). Conclusions: Our results suggest that levosimendan can be potentially protective for fibrotic liver and probably can prevent cirrhosis complication as cirrhotic cardiomyopathy and hepatic encephalopathy.

Artificial Intelligence (AI) play an important role in many fields, including medical education, practice, and research. Many medical educators started using ChatGPT at the end of 2022 for many purposes. The aim of this article was to explore the potential uses, benefits and risks of using ChatGPT in integrated pharmacotherapy of infectious disease module education. This study was an experimental study with content analysis of the potential applications of the ChatGPT model for integrated pharmacotherapy of infectious diseases module education was performed. The findings of this study shows that there are many potential uses, benefits and risks associated with the use ChatGPT. In conclusion, medical and health sciences educators can use ChatGPT as a guide in many aspects related to the integrated pharmacotherapy of infectious disease curriculum development, syllabus design, lecture notes preparation and exam preparation with caution.

Aging kills 100,000 people a day - more than any other cause of death combined. The exact causes of aging have been much discussed, but the most pressing issue with regard to aging appears to me to be lipofuscin accumulation. That is, the accumulation of indigestible cellular garbage that needs to be removed from our cells, then the body. In this piece, I will explain why I think “getting rid of the garbage” should be at least one of our main goals with regard to longevity research for now.

The purpose of this paper is to highlight the main themes and insights from the Journal of Orthopedic Research (JOR)/JOR Spine Workshop during the Orthopedic Research Society 2022 Annual Meeting in Tampa Bay, Florida. This workshop, organized by JOR Editor-in-Chief Dr. Linda Sandell, focused on communication strategies (particularly using social media) to broadcast published work in orthopedic research. In this manuscript, we summarize data that support the beneficial impacts of amplifying scholarly works on social media and outline a linearized workflow for constructing a Twitter posts, which can be generalized to other social media platforms, to share academic research. Finally, we identify resources to alleviate barriers to social media use and help promote professionalism and success online in the orthopedic research community. As early career scientists in orthopedics, we see immense value in using social media, particularly Twitter, to communicate our research findings and build our scholarly networks. We hope this information will be persuasive to those in the orthopedic field and be broadly applicable to others in related scientific fields who wish to disseminate findings and engage a public audience on social media. For the orthopedic research society and journal of orthopedic research, social media can assist in accomplishing our mission of creating a world without musculoskeletal limitations via the timely dissemination of orthopedic research findings and news.

Human serum albumin (HSA) is the ultimate, homeostatic determinant of fluid volume (FV) in all compartments of the body. The ability to change the pressure and flow of nutrient medium to cellular structures selectively has clinical significance in almost all areas of clinical medicine. We have shown that present fluid therapy (FT) using either colloid or saline dilutes nutrients. HSA binds and delivers nutrients, a lack of HSA binding causes Albumin Binding Disease (ABD) changing both colloidal pressure and nutrients leading to symptoms of sepsis. A reduction in HSA binding can be through lack of HSA or external ligands taking up binding sites on HSA. Many diseases cause ABD when immunoglobulins, infectious particles and by products bind to HSA including COVID-19 and other bacterial diseases like streptococcus as well as metabolic and cardiac disease due to incorrect pressure and nutrients. To raise HSA binding potential and remove vulnerabilities to these diseases we propose raising HSA. We show how present methods of fluid therapy (FT) are inefficient in that control of both pressure and nutrients forms initial equilibrium in the liver. HSA production and binding to nutrients is maintained at a level by the pressure in hepatocytes with the pancreatic and adrenal hormones moderating. Glucose and Ke-tone production are critical in the management of HSA binding and control of blood, colloidal pressure, and health of cells. Ketones provide a distinct mechanism of liver to lungs-heart metabolism during hypoglycaemia and activity. This known chain of nutrition becomes critical during disease like acute respiratory distress syndrome (ARDS) when ketones may be overproduced. HSA must therefore be infused into the liver to raise HSA levels safely. We investigated the control of HSA as a product of the actions of pressure in hepatocytes and changes in pancreatic and adrenal hormones. We found that in addition to pressure during glucose abundancy HSA is re-leased with ketones on administration of insulin and consider that this mechanism retains HSA moderation. HSA can therefore be increased by increasing insulin in the presence of glucose in the correct amounts. We suggest a protocol to increase FV, blood, lymph volume by infusion of HSA, insulin, and glucose direct to the liver so that the level of HSA stabilises. We suggest this will raise all other nutrients in the new FV, blood, lymph culminating in the creation of new blood cells. We propose that in a clinical situation maintaining this protocol will alleviate the symptoms of ABD and decrease the likelihood of serious illness and death.

Background: The effect of the COVID-19 pandemic has transformed medical education and is likely to have long-lasting effects on student learning, mental well-being, and eating behaviour. This study aimed to examine the learning behaviors of medical students at the American University of Integrative Sciences (AUIS), Barbados, during the COVID-19 pandemic. Methods: A cross-sectional web-based online survey was administered to medical students at AUIS from July until November 2021. The data collecting instrument recorded students’ demographic and learning behaviour information (Meo et al. 2020), and eating disorders (SCOFF questionnaire). Results: The overall response rate was 55% (n=120). In relation to learning behaviour, students agreed with the following statements: ‘deterioration in work performance and studying’ (48.4%), ‘remember subject’s contents appropriately’ (40.4%), ‘concentration on the studies’ (40.3%), ‘difficulty in performing two tasks simultaneously’ (38.7%), ‘difficulty in performing mental calculations’ (33.9%), ‘difficulty in recalling recent information’ (32.3%), and ‘difficulty in recalling old information’ (38.7%). Among the 8 dimensions of learning behaviors, deterioration in work performance or studying, and difficulties in recalling recent information were found to be significantly associated with the gender of the students. For SCOFF questionnaire, approximately 24.2% screened positive for eating disorders. Screening with the SCOFF test demonstrated that female, older (>25 years), overweight + obese, Clinical Sciences + PreMed, and non-USA-based students were at more risk of eating disorders. Conclusions: The results indicate that during the COVID-19 pandemic AUIS students have developed learning difficulties, and are likely to have eating disorders. University policymakers should take appropriate measures to support a healthy learning environment and improve students' mental well-being and eating behaviours.

Curcumin is a natural dietary polyphenol which that possesses potent anti-aging and neuroprotective properties through various mechanisms and signaling pathways. This study aimed to investigate the effect of curcumin on factors involved in neurogenesis and angiogenesis in the aged brain. Old female Wistar rats were divided into three equal groups (n=7): control, sham, and curcumin (received curcumin, i.p., 30 mg/kg and 5 days/week for 8 weeks) rats. Curcumin treatment caused a significant increase in the vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF) and anti-apoptotic protein BCl-2 in the brains of aging rats but no significant effect on anti-apoptotic Bax protein. Additionally, curcumin attenuated brain lipid peroxidation and decreased transforming growth factor β1 (TGF-β1). These results suggested that curcumin possesses neuroprotective effects against brain aging, which were mediated by improvment in neurogenesis and angiogenesis. Also, curcumin could alleviate brain aging which may be due to attenuating oxidative stress, inhibiting apoptosis and down-regulating TGF-β1, which in turn enhances VEGF and BDNF. Therefore, curcumin has potential therapeutic value in the treatment of neurological apoptosis, neurogenesis and angiogenesis changes caused by brain aging.

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.

A small proportion of health care users are recognised to use a significantly higher proportion of health system resources, largely due to systemic, inequitable access and disproportionate health burdens. These high-resource health system users are routinely characterised as older, with multiple comorbidities, and reduced access to adequate health care. Geographic trends also emerge, with more rural and isolated regions demonstrating higher rates of high-resource use than others. Despite known geographical discrepancies in health care access and outcomes, health policy and research initiatives remain focused on urban population centers. To alleviate mounting health system pressure from high-resource users, their characteristics must be better understood within the context in which it arises. To examine this, a scoping review was conducted to provide an overview of characteristics of high-resource users in rural and remote communities in Canada and Australia. In total, 21 papers were included in the review. Using qualitative thematic coding, primary findings characterised rural high-resource users as those of an older age; with increased comorbid conditions and condition severity; lower socioeconomic status; and elevated risk behaviours.

Depression and obesity are highly comorbid with one another, with evidence for bidirectional causal links between each disorder and a shared biological basis. The available evidence suggests that genetic factors play a major role in influencing both the occurrence of comorbid depression and obesity, their courses, and their response to existing treatments. The current paper is a scoping review of studies that have evaluated the contribution of specific genetic variants to the comorbidity between obesity and depression. Based on a search of the PubMed and EMBASE databases, 28 studies were included in this review, covering 54 candidate genes. Positive associations were identified for fourteen genetic loci (AKR1C2, APOA5, COMT, DAT1, FTO, KCNE1, MAOA, MC4R, MCHR2, NPY2R, NR3C1, Ob, PCSK9 and TAL1). Replicated findings across two or more independent samples were observed for the FTO and MC4R genes. Many of these gene products represent novel molecular targets for the pharmacological management of obesity which are not pharmacologically influenced by existing anti-obesity or antidepressant medications. The implications of these associations for future drug development are discussed, with an emphasis on recent evidence on the polygenic architecture of comorbid depression and obesity, and on a precision medicine approach to these conditions.

The aim of this study was to estimate the association between fear of COVID-19 and risk perception with preventive behavior in health professionals from three Latin American countries. An analytical cross-sectional study was conducted. Health professionals with on-site care in Colombia, Ecuador, Guatemala, and Peru were surveyed. Information was collected through an online self-report questionnaire. The main variables were preventive behavior as the dependent variable and fear of COVID-19 and risk perception as independent variables. Linear regression was used, and Beta coefficients and p-values were calculated. 435 health professionals were included, the majority were aged 42 years or older (45.29%, 95%CI: 40.65%-50.01%) and female (67.82%, 95%CI: 63.27%-72.05%). It was shown that the greater the fear of COVID-19, the greater the preventive behavior of COVID-19 infection (B=2.21, p=0.002 for total behavior; B=1.12, p=0.037 for additional protection at work; B=1.11, p

Introduction: The rapid emergence of COVID-19 as a global crisis has led to the approval of many vaccinations, which were unfortunately associated with high complication rates due to a lack of sufficient safety studies. Objectives: The following manuscript focuses on discussing the demyelinating disorders that were noticed after COVID vaccine administration. Methods: We conducted a retrospective study using anonymous medical records from the US vaccine adverse events reporting system, complications retrieved included Acute disseminated encephalomyelitis (ADEM), Guillain Barre syndrome (GBS), and Multiple sclerosis (MS), outcome parameters were age, sex and the dose after which this complication was observed. Patients younger than 18 years-old were excluded as some of the vaccines, namely Janssen (JNJ-78436735) is not yet approved below this age. Results: Our analysis showed that demyelinating disorders were more likely to occur in patients over the age of 50 compared to other age groups, regardless of the type of vaccination, except for MS and ADEM occurrences after the Jansen vaccine. In addition, demyelinating complications were more likely to occur after the first dose of vaccination. Conclusion: Further research and observation of demyelinating diseases in different vaccinations, as well as additional in vitro studies, are recommended to further explain the pathogenesis of demyelinating disorder occurrence.

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms towards the foreign material silicone. The aim of this work was to understand the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intraindividual relative quantitation TMT-liquid chromatography–tandem mass spectrometry approach was applied to the profile wound proteome formed around SMI in the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to a functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation, which were adsorbed to SMI surfaces after 6–8 months. Characterization of the expander-adhesive proteome by a label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.

The effect of SARS-CoV-2 pandemic has been subsided significantly following the rapid development of vaccine. However, patients with cancer and immunosuppressed state, who are more prone to mortality and morbidity due to this infection, were excluded from majority of the vaccine trials. Moreover, suggested dose modification for cancer and immunosuppressed patients are often not followed because of lack of awareness or unavailability of vaccination schedule. This review will try to bridge this knowledge gap by summarizing the current suggestions of dose modification of COVID-19 vaccine for patients with cancer and immunosuppression.

Cells produce reactive oxygen species (ROS) as by-products of metabolism, which can give rise to a two-sided effect on the body under balanced and imbalanced oxidant homeostasis conditions. Antioxidant supplements exert their beneficial efficacy in the treatment of metabolic diseases only when the oxidant homeostasis is imbalanced with the over-production of ROS. Over-supplementation of antioxidant(s) can also cause an imbalanced oxidant homeostasis to exert detriments to the induction of metabolic diseases. This commentary raises a concern that prior to precise supplementation of antioxidants, an establishment of oxidant homeostasis status is required in avoiding an imbalanced oxidant homeostasis in vivo. In searching for valid oxidant stress makers, 3-Nitrotyrosine seems to fit in with the selection criteria and its quantification can be correlated with the degree of oxidative stress in vivo.

Background The main reason for the worldwide massive covid vaccination in 2021 was to reduce the high mortality caused by the Covid-19 virus in 2020. It is time that in 2022 a rigorous analysis is done of the effectiveness of this massive vaccination. Methods In statistics, we have an accurate methodology to measure the impact of massive vaccination on public health. The mathematical relation between vaccinated/alive groups will be repeated between vaccinated/dead groups with high statistical certainty. This occurs because we are dealing with big numbers. Results Calculations were done for five periods of four weeks: weeks 35-38 (2021), weeks 39-42 (2021), weeks 43-46 (2031), weeks 47-50 (2021), and weeks 51(2021)-2(2022). Obtained results are confirming that the mortality of the vaccinated infected groups is higher on average by 14.5% than the mortality of non-vaccinated infected groups. Conclusions Results are suggesting the extension of the statistic between the vaccinated/alive group and the vaccinated/dead group for different age groups. These statistics will have higher statistical significance because of the elimination of the Simpson effect. Calculating the exact impact of covid-19 vaccination on the mortality rate is the necessary step to satisfy the first principle of medicine: “Primum non nocere”.

In diabetic foot infections (DFI), the clinically virulence of skin commensals are generally pre-sumed to be of low virulence. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria); and, pyogenicpathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1,018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pyogenicpathogenic patho-gens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxy-gen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs 24 %, p=0.23) or microbiological recurrence (11% vs 17 %, p=0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confi-dence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may equally base on oral non-beta-lactam antibiotic agents susceptible to the corresponding skin pathogens.

Background: Osteoarthritis is the most common degenerative joint disease resulting in pain and altered joint function. Objective: We investigated the possible association between serum interleukin-6 and symptoms of knee osteoarthritis with regard to pain, stiffness, physical function, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We also examined the connections between serum interleukin-6 and radiographic severity in primary knee osteoarthritis patients. Methods: In this case-control study, fifty primary knee osteoarthritis patients and fifty age and sex matched controls were randomly recruited. Serum interleukin-6 levels were immunoassayed in patients’ and controls’ serum. Patients’ knee pain, stiffness and physical function were assessed by the respective subscales of the WOMAC Index. Standing anteroposterior radiographs of the knee joint were performed and graded with the Kellegren-Lawrence grade. Results: The mean serum IL-6 level was significantly higher in osteoarthritis patients (110.22 ± 46.98pg/ml) than controls (46.04 ± 12.34 pg/ml) (p=0.001). The WOMAC Index in patients ranged from 0 – 95 and the Kellegren-Lawrence score mean was 2.7 ± 0.76. There was a significant correlation between serum IL-6 levels and pain (r=0.595 p=0.001), physical function score (r=0.666, p=0.001)), and the radiographic score (r=0.799, p=0.001). Regression analysis showed that IL-6 level had a greater impact on both the WOMAC Index (p=0.005) and the Kellegren-Lawrence score (p=0.01). Conclusion: Serum IL-6 level is increased in primary knee osteoarthritis patients. Also, serum interlukin-6 is significantly related to osteoarthritis symptoms and radiographic severity.

Background and Objectives: he treatment of large bone defects in geriatric patients often presents a major surgical challenge because of age-related bone loss. In such patients, the scarcity of healthy makes autologous grafting techniques hard to perform. On the one hand, clinicians’ fear of possible infections limits using bone substitute materials (BSM). On the other hand, BSM is limitless and spares patients another surgery to harvest autologous material. Materials and Methods: To address the aptness of BSM in geriatric patients, we performed a retrospective analysis of all patients over the age of 64 years who visited our clinic between the years 2011–2018. The study assessed postoperative complications clinically and healing results radiologically. The study included 83 patients with bone defects at the distal radius, proximal humerus, and proximal tibia. The defect zones were filled with BSM based on either nanocrystalline hydroxyapatite (NHA) or calcium phosphate (CP). For comparison, a reference group (empty defect, ED) without the void filling with a BSM was also included. Results: 106 patients sustained traumatic fractures of the distal radius (71.7%), proximal humerus (5.7%), and proximal tibia (22.6%). No difference was found between the BSM groups in infection occurrence (p = 1.0). Although not statistically significant, the BSM groups showed a lower rate of pseudarthrosis (p = 0.09) compared with the ED group. Relative risk (RR) of complications was 32.64% less in the BSM groups compared with the ED group. The additional beneficial outcome of BSM was demonstrated by calculating the number needed to treat (NNT). The calculation showed that with every six patients treated, at least one complication could be avoided. Radiological assessment of bone healing showed significant improvement in the bridging of the defect zone (p < 0.001) when BSM was used. Conclusions: In contrast to previous studies, the study showed that BSM could support bone healing and does not present an infection risk in geriatric patients. The NNT calculation indicates a wider potential benefit of BSM.

(1) Background: This work aimed to conduct a comparative study, providing long-term data about patient-reported outcome measures and donor site scar assessments, as well as an aesthetic evaluation of the reconstructed breasts in patients with DIEP versus PAP flap breast reconstruction. (2) Methods: This prospective, single-center, matched cohort study included a total of 36 patients after DIEP and PAP flap breast reconstruction. The evaluation was carried out using the Breast-Q and POSAS questionnaire, as well as the Breast Aesthetic Scale for cosmetic analysis, by four plastic surgeons. (3) Results: The postoperative Breast-Q evaluation revealed no significant differences between both patient groups for the categories of the physical well-being of the donor site, the physical well-being of the breast, and satisfaction with the breast. A scar evaluation of the donor site region showed equivalent results for the thigh and abdomen regions, concerning the overall opinion of the patients and the observers. There was no significant difference between both methods of reconstruction for all aspects of breast aesthetics. (4) Conclusions: Similar results for donor site morbidity, scar quality, and the aesthetic outcome of the breasts in both the DIEP and PAP patient groups have been demonstrated. Hence, in those cases suitable for both types of reconstruction, the decision can be based on factors such as patients’ lifestyles, leisure activities, and preferences.