A historical and palaeopathological perspective on cancer.

Cancer is often wrongly considered to be a modern disease in many popular medical venues. Cancers have been known to humanity since ancient times. In fact, its antiquity can be identified through the application of palaeopathological methodologies. The present perspective demonstrates by means of a historical and palaeopathological analysis how oncological manifestations were present long before the emergence of anatomically modern humans and addresses the epidemiological transition from ancient times to the contemporary world. The final section of the article examines breast cancer and its identification in ancient human remains.

The Evolution of Diagnostic Techniques in the Paleopathology of Tuberculosis: A Scoping Review.

Tuberculosis (TB) is an ancient chronic infectious disease that remains a global health concern. In human remains, the most common and characteristic clinical signs are the skeletal modifications involving the spine, such as in Pott's disease. Diagnosing TB in ancient human remains is challenging. Therefore, in this systematic review, the authors investigated the studies assessing molecular diagnosis of Pott's disease in ancient human remains with the intention to survey the literature, map the evidence, and identify gaps and future perspectives on TB in paleopathology. Our systematic review offers a full contextualization of the history of Pott's disease in ancient times. Our search strategy was performed between August 2022 and March 2023. The authors initially identified 340 records, and 74 studies were finally included and assessed for qualitative analysis. Due to non-specific clinical signs associated with TB, how best to diagnose tuberculosis in human remains still represents a central point. Nevertheless, ancient DNA (aDNA) analysis, lipid biomarkers, and spoligotyping might be extremely useful tools in the study of TB in human remains. Moreover, we propose the extraction and study of immune response genes involved in innate and adaptive immunity versus Mycobacterium spp. as an innovative and vastly overlooked approach in TB paleopathology. Complementary methodologies should be integrated to provide the best approach to the study of TB in human remains.

A Systematic Review of Varying Definitions and the Clinical Significance of Fredet's Fascia in the Era of Complete Mesocolic Excision.

BACKGROUND: Fredet's fascia represents a crucial landmark for vascular surgical anatomy, especially in minimally invasive complete mesocolic excision (CME) for right-sided colon adenocarcinoma. Fredet's fascia allows access to the gastrocolic trunk of Henle (GCTH), the most critical step in both open and minimally invasive right-sided CME techniques. Despite this, a recent workshop of expert surgeons on the standardization of the laparoscopic right hemicolectomy with CME did not recognize or include the term of Fredet's fascia or area. Hence, we undertook a systematic review of articles that include the terms "Fredet's fascia or area", or synonyms thereof, with special emphasis on the types of articles published, the nationality, and the relevance of this area to surgical treatments. METHODS: We conducted a systematic review up to 15 July 2022 on PubMed, WOS, SCOPUS, and Google Scholar. RESULTS: The results of the study revealed that the term "Fredet's fascia" is poorly used in the English language medical literature. In addition, the study found controversial and conflicting data among authors regarding the definition of "Fredet's fascia" and its topographical limits. CONCLUSIONS: Knowledge of Fredet's fascia's surgical relevance is essential for colorectal surgeons to avoid accidental injuries to the superior mesenteric vascular pedicle during minimally invasive right hemicolectomies with CME. In order to avoid confusion and clarify this fascia for future use, we suggest moving beyond the use of the eponymous term by using a "descriptive term" instead, based on the fascia's anatomic structure. Fredet's fascia could, therefore, be more appropriately renamed "sub-mesocolic pre-duodenopancreatic fascia".

Pyrrolyl and Indolyl α-γ-Diketo Acid Derivatives Acting as Selective Inhibitors of Human Carbonic Anhydrases IX and XII.

Solid tumors are active tissues containing hypoxic regions and producing metabolic acids. By decreasing pH, cancer cells create a hostile environment for surrounding host cells and foster tumor growth and progression. By governing acid/base regulation, carbonic anhydrases (CAs) are involved in several physiological/pathological processes, including tumors. Indeed, CAs are clinically relevant in cancer therapy as among the fifteen human isoforms, two of them, namely CA IX (overexpressed in solid tumors and associated with increased metastasis and poor prognosis) and CA XII (overexpressed in some tumors) are involved in tumorigenesis. Targeting these two isoforms is considered as a pertinent approach to develop new cancer therapeutics. Several CA inhibitors (CAIs) have been described, even though they are unselective inhibitors of different isoforms. Thus, efforts are needed to find new selective CAIs. In this work, we described new diketo acid derivatives as CAIs, with the best acting compounds 1c and 5 as nanomolar inhibitors of CA IX and XII, being also two orders of magnitude selective over CAs I and II. Molecular modeling studies showed the different binding poses of the best acting CAIs within CA II and IX, highlighting the key structural features that could confer the ability to establish specific interactions within the enzymes. In different tumor cell lines overexpressing CA IX and XII, the tested compounds showed antiproliferative activity already at 24 h treatment, with no effects on somatic not transformed cells.

Efficient Hydrogenation of N-Heterocycles Catalyzed by NNP-Manganese(I) Pincer Complexes at Ambient Temperature.

Manganese-catalyzed hydrogenation reactions have aroused widespread interest in recent years. Among the catalytic systems described, especially PNP- and NNP-Mn pincer catalysts have been reported for the hydrogenation of aldehydes, ketones, nitriles, aldimines and esters. Furthermore, NNP-Mn pincer compounds are efficient catalysts for the hydrogenolysis of less reactive amides, ureas, carbonates, and carbamates. Herein, the synthesis and application of specific imidazolylaminophosphine ligands and the corresponding Mn pincer complexes are described. These new catalysts have been characterized and studied by a combination of experimental and theoretical investigations, and their catalytic activities have been tested in several hydrogenation reactions with good to excellent performance. Especially, the reduction of N-heterocycles can be performed under very mild conditions.

Canaloplasty in Pseudoexfoliation Glaucoma. Can It Still Be Considered a Good Choice?

Purpose: The aim of this study was to assess the long-term outcomes of canaloplasty surgery in pseudoexfoliation glaucoma (PEXG) patients. Material and Methods: A total of 116 PEXG patients with an intraocular pressure (IOP) > 21 mm/Hg and maximum tolerated local medical therapy who underwent canaloplasty from February 2008 to January 2022 were considered. Every six months, all subjects underwent a complete ophthalmic examination. The period of follow-up ranged from 2 to 167 months. Inclusion criteria included only patients for whom the entire procedure could be completed with a follow-up of at least 2 years. Results: Amongst the 116 PEXG patients, the entire procedure could not be performed in 10 eyes (8.6%), and thus they were not considered in the analysis. Twenty-three patients did not reach the two-year follow-up and another 16 patients during this time period were lost. A total of 67 patients with a mean follow-up of 49 ± 32.3 months were considered in the analysis. The pre-operative mean IOP was 31.2 ± 8.7 mm/Hg (range 20−60). The mean IOP at the two-year follow-up was 17.2 ± 6.7 mmHg, with a mean reduction from baseline of 44.9%. After two years, the qualified success rates according to three different criteria (IOP ≤ 21, ≤18 and ≤16 mmHg) were 80.6%, 73.1% and 61.0%, respectively. The total number of medications used pre- and at the follow-up at 2 years was 3.5 ± 0.8 and 1.2 ± 1.4, respectively. Early complications included: hyphema, in about 30% of cases; Descemet membrane detachment (4.9%); and IOP spikes > 10 mmHg (9.7%). A late failure with an acute IOP rise of up to 50 mmHg was observed in 41 cases (61.2%) after 3 to 72 months. Conclusions: Long-term post-operative outcomes of canaloplasty in PEXG patients appear to be quite good on average; however, an acute rise in IOP can be observed in more than 60% of the cases after a long period of satisfactory IOP control. For this reason, canaloplasty may not be suitable in eyes with PEXG, especially in patients with severe functional damage.

360° Ab-Interno Schlemm's Canal Viscodilation with OMNI Viscosurgical Systems for Open-Angle Glaucoma-Midterm Results.

PURPOSE: To evaluate the effectiveness of ab-interno microcatheterization and 360° viscodilation of Schlemm's canal (SC) performed with OMNI viscosurgical system in open angle glaucoma (OAG) together or not with phacoemulsification. SETTING: Two surgical sites. DESIGN: Retrospective, observational. METHODS: Eighty eyes from 73 patients with mild to moderate OAG underwent ab- interno SC viscodilation performed with OMNI system. Fifty eyes (Group 1) underwent only SC viscodilation, while 30 eyes (Group 2) underwent glaucoma surgery + cataract extraction. Primary success endpoint at 12 months was an intraocular pressure (IOP) reduction higher than 25% from baseline with an absolute value of 18 mmHg or lower, either on the same number or fewer ocular hypotensive medications, without further interventions. Secondary effectiveness endpoints included mean IOP, number of medications and comparison of outcomes between groups. Safety endpoints consisted of best-corrected visual acuity (BCVA), adverse events (AEs), and subsequent surgical procedures. RESULTS: Primary success was achieved in 40.0% and 67.9% in Groups 1 and 2, respectively. Mean IOP at 12-month follow-up showed a significant reduction in both groups (from 23.0 to 15.6 mmHg, p < 0.001, and from 21.5 to 14.1, p < 0.001, in Groups 1 and 2, respectively). Mean medication number decreased in both groups (from 3.0 to 2.0, p < 0.001 and from 3.4 to 1.9, p < 0.001, in Groups 1 and 2, respectively). AEs included hyphema (2 eyes), mild hypotony (4 eyes), IOP spikes one month after surgery (1 eye). Twelve eyes (15.0%) required subsequent surgical procedures. No BCVA reduction was observed. CONCLUSIONS: Viscodilation of SC using OMNI viscosurgical systems is safe and relatively effective in reducing IOP in adult patients with OAG.

Trimethylamine N-oxide (TMAO): a new attractive target to decrease cardiovascular risk.

Cardiovascular disease (CVD) is one of the greatest disease burdens and takes the lives of many each year. There are many risk factors both modifiable and non-modifiable which contribute to the onset and progression of the disease. Trimethylamine N-oxide (TMAO) in recent years has been found to have a correlation with CVD onset. Those with increased levels of the metabolite have a markedly increased risk of future development of cardiometabolic disorders.This literature review aimed to critique past studies undertaken to find a consensus of the significance of the interrelationship between TMAO and cardiovascular risk. A definite link between TMAO levels and a CVD outcome was found. The majority of the literature stated the relationship with evidence; however, there is still some uncertainty as to why and how the correlation occurs. Further study needs to be done to further dissect and understand the relationship between TMAO and CVD risk.

Role of PLCγ1 in the modulation of cell migration and cell invasion in glioblastoma.

Phosphoinositide-specific phospholipases C (PLCs) are a class of enzymes involved in several cell activities, such as cell cycle regulation, proliferation, differentiation and cytoskeletal dynamics. Among these enzymes, PLCγ1 is one of the most expressed PLCs in the brain, contributing to a complex network in the developing nervous system. Several studies have shown that PLCγ1 signaling imbalance is linked to several brain disorders, including glioblastoma, the most aggressive brain tumor in adults. Indeed, it has been demonstrated a link between PLCγ1 inhibition and the arrest of glioma cell motility of fetal rat brain aggregates and the impairment of cell invasion abilities following its down-regulation. This study aims to determine the pathological influence of PLCγ1 in glioblastoma, through a translational study which combines in silico data, data from glioblastoma patients' samples and data on engineered cell lines. We found out that PLCγ1 gene expression correlates with the pathological grade of gliomas, and it is higher in fifty patients' glioblastoma tissue samples compared to twenty healthy controls. Moreover, it was demonstrated that PLCγ1 silencing in U87-MG leads to a reduction in cell migration and invasion abilities. The opposite trend was observed following PLCγ1 overexpression, suggesting an interesting possible involvement of PLCγ1 in gliomas' aggressiveness.

One year of anatomy teaching and learning in the outbreak: Has the Covid-19 pandemic marked the end of a century-old practice? A systematic review.

At the end of 2019, the Covid-19 pandemic spread caused restrictions in business and social spheres. Higher education was also severely affected: universities and medical schools moved online to distance learning and laboratory facilities closed. Questions arise about the long-term effects of this pandemic on anatomical education. In this systematic review, the authors investigated whether or not anatomical educators were able to deliver anatomical knowledge during this pandemic. They also discuss the challenges that anatomical education has faced over the last year. The search strategy was conducted between July 2020 and July 2021. Two hundred and one records were identified, and a total of 79 studies were finally included. How best to deliver anatomy to students remains a moot point. In the last years, the advent of new technologies has raised the question of the possible overcoming of dissection as the main instrument in anatomical education. The Covid-19 pandemic further sharpened the debate. Remote learning enhanced the use of technologies other than cadaveric dissection to teach anatomy. Moreover, from the analyzed records it appears that both from students' perspective as well as teachers' there is a clear tear between those who endorse dissection and those who believe it could be easily overcome or at least integrated by virtual reality and online learning. The authors strongly believe that the best anatomy teaching practice requires the careful adaptation of resources and methods. Nevertheless, they support cadaveric dissection and hope that it will not be replaced entirely as a result of this pandemic.

Could Physical Activity Have any Role in Cardiovascular Disease Prevention in Prisoners? A Systematic Review.

More than 10.74 million people are currently held in penal institutions worldwide. Moreover, there is also evidence that the percentage of elder and female prisoners has been consistently growing. Cardiovascular diseases are the leading cause of death worldwide. Exercise training and physical activity help to prevent both primary and secondary cardiovascular events. Data on the influence of physical activity on the well-being in prison population is scarce. Here, we discussed, in a systematic review, the general health conditions and the cardiovascular risk profile in the prisoners compared to the general population and evaluated whether or not exercise could be a valuable tool in preventing these diseases in inmates. We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement: 769 were initially identified, and a total of 24 studies were finally included. Nine studies evaluated the health conditions in prisoners, five studies evaluated the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) in the prison population, and 10 studies evaluated the feasibility and the effectiveness of exercise programs in prisoners. Sports-educational programs can benefit prison inmates. It appears that supervised exercise training is an effective coping strategy to deal with incarceration. Moreover, it seems the sports programs might be a useful tool in improving physical and mental health of prisoners as well as in decreasing cardiovascular risk factors.

The Ability of Nutrition to Mitigate Epigenetic Drift: A Novel Look at Regulating Gene Expression.

Epigenetic drift causes modification in gene expression during aging and a myriad of physiological changes that are mostly undesirable, remove youthful phenotype and are related to biological decay and disease onset. The epigenome is considered a stable regulator of genetic expression. Moreover, evidence is now accumulating that commonly available compounds found in foods can influence the epigenome to embrace a more youthful and therefore, more disease resistant state. Here we explore the correlation between nutriment and the epigenetic regulation through various types of alimentation. The aim is not to discuss specific chemicals involved in disease onset. Instead, we offer a brief glance at pathogens and offer a practical pathway into epigenetic regulation, hypothesizing that epigenetic drift might be attenuated by several foods able to drive a more youthful and disease resistant phenotype.

Canaloplasty in Pigmentary Glaucoma: Long-Term Outcomes and Proposal of a New Hypothesis on Its Intraocular Pressure Lowering Mechanism.

This study presents the long-term results on canaloplasty in a group of patients affected by pigmentary glaucoma, and studies the progression of the disease after surgery. MATERIAL AND METHODS: Twenty-nine eyes of 25 patients with pigmentary glaucoma in maximum tolerated medical therapy with significant visual field damage progression underwent canaloplasty and were followed up to 11 years (mean 59.8 ± 30.1 months). All patients underwent a complete ophthalmic examination every 6 months. RESULTS: The pre-operative mean intraocular pressure (IOP) was 31.8 mmHg ± 10.9 (range 21-70) with an average of 3.3 medications. After 1, 2, 3, and 4 years, the mean IOP was 15.9 ± 4.0, 14.4 ± 7.3, 14.1 ± 2.1, and 15.7 mmHg, respectively, with 0.4, 0.5, and 0.7 medications, respectively. Four patients underwent trabeculectomy after 3 to 30 months due to uncontrolled IOP. Gonioscopy showed a significant reduction of pigment in trabecular meshwork in all cases, starting from the sixth month. In some cases, the pigment was almost completely reabsorbed after two years, suggesting an accelerated transit and escape of the granules through the trabecular spaces. CONCLUSIONS: Canaloplasty seems to be a reasonable option in treating patients affected by progressive pigmentary glaucoma. The reabsorption of pigment granules from the trabecular meshwork could, at least in part, explain the relatively high success rate observed after this surgical procedure.

Homogeneous and heterogeneous catalytic reduction of amides and related compounds using molecular hydrogen.

Catalytic hydrogenation of amides is of great interest for chemists working in organic synthesis, as the resulting amines are widely featured in natural products, drugs, agrochemicals, dyes, etc. Compared to traditional reduction of amides using (over)stoichiometric reductants, the direct hydrogenation of amides using molecular hydrogen represents a greener approach. Furthermore, amide hydrogenation is a highly versatile transformation, since not only higher amines (obtained by C-O cleavage), but also lower amines and alcohols, or amino alcohols (obtained by C-N cleavage) can be selectively accessed by fine tuning of reaction conditions. This review describes the most recent advances in the area of amide hydrogenation using H2 exclusively and molecularly defined homogeneous as well as nano-structured heterogeneous catalysts, with a special focus on catalyst development and synthetic applications.

Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review.

Some random mutations can confer a selective advantage to a hematopoietic stem cell. As a result, mutated hematopoietic stem cells can give rise to a significant proportion of mutated clones of blood cells. This event is known as "clonal hematopoiesis." Clonal hematopoiesis is closely associated with age, and carriers show an increased risk of developing blood cancers. Clonal hematopoiesis of indeterminate potential is defined by the presence of clones carrying a mutation associated with a blood neoplasm without obvious hematological malignancies. Unexpectedly, in recent years, it has emerged that clonal hematopoiesis of indeterminate potential carriers also have an increased risk of developing cardiovascular disease. Mechanisms linking clonal hematopoiesis of indeterminate potential to cardiovascular disease are only partially known. Findings in animal models indicate that clonal hematopoiesis of indeterminate potential-related mutations amplify inflammatory responses. Consistently, clinical studies have revealed that clonal hematopoiesis of indeterminate potential carriers display increased levels of inflammatory markers. In this review, we describe progress in our understanding of clonal hematopoiesis in the context of cancer, and we discuss the most recent findings linking clonal hematopoiesis of indeterminate potential and cardiovascular diseases.