Land Bridges and Rafting Theories to Explain Terrestrial-Vertebrate Biodiversity on Madagascar.

Madagascar's celebrated land-vertebrate assemblage has long been studied and discussed. How the ancestors of the 30 different lineages arrived on the island, which has existed since 85 Mya and is separated from neighboring Africa by 430 km of water, is a deeply important question. Did the colonizations take place when the landmass formed part of Gondwana, or did they occur later and involve either now-drowned causeways or overwater dispersal (on vegetation rafts or by floating/swimming)? Following a historical review, we appraise the geological-geophysical evidence and the faunal-suite colonization record. Twenty-six of the clades are explained by temporally stochastic overwater dispersals, spanning 69-0 Mya, while two others are considered Gondwanan vicariant relicts. Due to a lack of information, the remaining two groups cannot be evaluated. The findings thus appear to resolve a debate that has rumbled along, with sporadic eruptions, since the mid-1800s.

The predictive and prognostic value of risk factors in patients receiving hybrid coronary revascularization with postoperative pulmonary complications.

Background: The mortality rate of coronary artery disease ranks first in developed countries, and coronary revascularization therapy is an important cornerstone of its treatment. The postoperative pulmonary complications (PPCs) in patients receiving one-stop hybrid coronary revascularization (HCR) aggravate the dysfunction of multiple organs such as the heart and lungs, therefore increasing mortality. However, the risk factors are still unclear. The objective of this study was to explore the risk factors of PPCs after HCR surgery. Methods: In this study, the perioperative data of 311 patients undergoing HCR surgery were reviewed. All patients were divided into two groups according to whether the PPCs occurred. The baseline information and surgery-related indicators in preoperative laboratory examination, intraoperative fluid management, and anesthesia management were compared between the two groups. Results: Advanced age [odds ratio (OR): 1.065, 95% confidence interval (CI): 1.030-1.101, P<0.001], high body mass index (BMI; OR: 1.113, 95% CI: 1.011-1.225, P=0.02), history of percutaneous coronary intervention (PCI) surgery (OR: 2.831, 95% CI: 1.388-5.775, P=0.004), one-lung volume ventilation (OR: 3.804, 95% CI: 1.923-7.526, P<0.001), inhalation of high concentration oxygen (OR: 3.666, 95% CI: 1.719-7.815, P=0.001), the application of positive end-expiratory pressure (PEEP; OR: 2.567, 95% CI: 1.338-4.926, P=0.005), and long one-lung ventilation time (OR: 1.015, 95% CI: 1.006-1.023, P=0.001) may be risk factors for postoperative PPCs in patients undergoing one-stop coronary revascularization surgery. Using the above seven factors to jointly predict the risk of PPCs in patients undergoing one-stop coronary revascularization surgery, the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) =0.873, 95% CI: 0.835-0.911, sensitivity: 84.81%, and specificity: 75.82%; the predictive model was shown to be effective. Conclusions: Patients undergoing HCR surgery with advanced age, high BMI, a history of PCI surgery, one-lung volume ventilation, inhalation of high concentration oxygen, use of PEEP, and prolonged single lung ventilation are more prone to PPCs.

What Is the Influence of HIV Serostatus on HbA1c? A Prospective Analysis Using Continuous Glucose Monitoring.

OBJECTIVE: Type 2 diabetes (T2D) is reported to be more common in people living with HIV (PLWH). Clinical guidelines recommend screening for diabetes in PLWH, but there is no agreed method due to studies reporting HbA1c is falsely low in PLWH. These studies were performed in the early HIV era when participants were taking older preparations of antiretroviral therapy that are rarely used today. We aimed to investigate whether HIV serostatus influences HbA1c. RESEARCH DESIGNS AND METHODS: We conducted a prospective cohort study of PLWH and age- and sex-matched HIV-negative participants who were purposely recruited from clinics in Brighton, U.K. Each participant wore a Dexcom G6 continuous glucose monitor (CGM) for up to 10 days, had glucose measured during an oral glucose tolerance test, and fructosamine and paired HbA1c were measured. We performed regression analysis to assess the influence of HIV on HbA1c and used a separate model for CGM glucose, venous glucose, and fructosamine. In addition, we included predictor variables used in previous studies that explored HbA1c discrepancy. RESULTS: We recruited 60 PLWH (90% men, 50% with T2D, mean ± SD age 57 ± 10.7 years, 100% undetectable viral load) and 48 people without HIV (92% men, 30% with T2D, mean age 57.7 ± 8.9 years). We found that HIV serostatus did not have a significant influence on HbA1c within the regression models. CONCLUSIONS: We performed a comprehensive assessment of glycemia to assess whether HIV serostatus influences HbA1c. We did not find any strong evidence that HIV serostatus influenced HbA1c. The results of our study support incorporating HbA1c into routine clinical blood work in PLWH.

Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

BACKGROUND: The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. STUDY DESIGN AND METHODS: A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). RESULTS: Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. CONCLUSION: Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

Removal of stuck tunnelled dialysis line requiring cardiopulmonary bypass and venous repair.

Tunnelled central venous dialysis catheters can usually be removed easily. However, their removal can become rarely complicated requiring more invasive techniques. We report a case in which cardiopulmonary bypass and repair of great veins was required for safe removal. A 38-year-old female with end-stage renal failure and a 3-year-old Hickman line inserted into her right internal jugular vein was referred to our cardiac surgical unit following failed attempts of line removal by local vascular surgical team using open vascular surgical techniques. As a result, an MDT decision was made that it was safer to proceed to a cardiothoracic surgical approach rather than other techniques. Investigations showed significant calcification surrounding the line which was adherent to the venous wall. Removal of the retained catheter required median sternotomy and the use of cardiopulmonary bypass as the great veins had to be opened to free the line and allow complete removal. The line was successfully removed with its encircling calcified sheath, and the veins were closed primarily without needing a patch repair. The integrity of the great veins was maintained to meet the on-going need this young patient has for central venous access. The patient made an uneventful recovery. When other measures fail, sternotomy and cardiopulmonary bypass provide a safe option for complete removal of stuck central venous catheters with low risk to the patient.

Prosthesis-Patient Mismatch and Aortic Root Enlargement: Indications, Techniques and Outcomes.

Prosthesis-patient mismatch (PPM) is defined as implanting a prosthetic that is insufficiently sized for the patient receiving it. PPM leads to high residual transvalvular gradients post-aortic valve replacement and consequently results in left ventricular dysfunction, morbidity and mortality in both the short and long term. Younger patients and patients with poor preoperative left ventricular function are more vulnerable to increased mortality secondary to PPM. There is debate over the measurement of valvular effective orifice area (EOA) and variation exists in how manufacturers report the EOA. The most reliable technique is using in vivo echocardiographic measurements to create tables of predicted EOAs for different valve sizes. PPM can be prevented surgically in patients at risk through aortic root enlargement (ARE). Established techniques include the posterior enlargement through Nicks and Manouguian procedures, and aortico-ventriculoplasty with the Konno-Rastan procedure, which allows for a greater enlargement but carries increased surgical risk. A contemporary development is the Yang procedure, which uses a Y-shaped incision created through the non- and left-coronary cusp commissure, undermining the nadirs of the non- and left-coronary cusps. Early results are promising and demonstrate an ability to safely increase the aortic root by up to two to three sizes. Aortic root enlargement thus remains a valuable and safe tool in addressing PPM, and should be considered during surgical planning.

Minimal-Access Coronary Revascularization: Past, Present, and Future.

Minimal-access cardiac surgery appears to be the future. It is increasingly desired by cardiologists and demanded by patients who perceive superiority. Minimal-access coronary artery revascularisation has been increasingly adopted throughout the world. Here, we review the history of minimal-access coronary revascularization and see that it is almost as old as the history of cardiac surgery. Modern minimal-access coronary revascularization takes a variety of forms-namely minimal-access direct coronary artery bypass grafting (MIDCAB), hybrid coronary revascularisation (HCR), and totally endoscopic coronary artery bypass grafting (TECAB). It is noteworthy that there is significant variation in the nomenclature and approaches for minimal-access coronary surgery, and this truly presents a challenge for comparing the different methods. However, these approaches are increasing in frequency, and proponents demonstrate clear advantages for their patients. The challenge that remains, as for all areas of surgery, is demonstrating the superiority of these techniques over tried and tested open techniques, which is very difficult. There is a paucity of randomised controlled trials to help answer this question, and the future of minimal-access coronary revascularisation, to some extent, is dependent on such trials. Thankfully, some are underway, and the results are eagerly anticipated.

Graft function and incidence of cardiac allograft vasculopathy in donation after circulatory-determined death heart transplant recipients.

Experience in donation after circulatory-determined death (DCD) heart transplantation (HTx) is expanding. There is limited information on the functional outcomes of DCD HTx recipients. We sought to evaluate functional outcomes in our cohort of DCD recipients. We performed a single-center, retrospective, observational cohort study comparing outcomes in consecutive DCD and donation after brain death (DBD) HTx recipients between 2015 and 2019. Primary outcome was allograft function by echocardiography at 12 and 24 months. Secondary outcomes included incidence of cardiac allograft vasculopathy, treated rejection, renal function, and survival. Seventy-seven DCD and 153 DBD recipients were included. There was no difference in left ventricular ejection fraction at 12 months (59% vs 59%, P = .57) and 24 months (58% vs 58%, P = .87). There was no significant difference in right ventricular function at 12 and 24 months. Unadjusted survival between DCD and DBD recipients at 5 years (85.7% DCD and 81% DBD recipients; P = .45) was similar. There were no significant differences in incidence of cardiac allograft vasculopathy (odds ratio 1.59, P = .21, 95% confidence interval 0.77-3.3) or treated rejection (odds ratio 0.60, P = .12, 95% confidence interval 0.32-1.15) between DBD and DCD recipients. Post-transplant renal function was similar at 1 and 2 years. In conclusion, cardiac allografts from DCD donors perform similarly to a contemporary population of DBD allografts in the medium term.

The colonisation of Madagascar by land-bound vertebrates.

Despite discussions extending back almost 160 years, the means by which Madagascar's iconic land vertebrates arrived on the island remains the focus of active debate. Three options have been considered: vicariance, range expansion across land bridges, and dispersal over water. The first assumes that a group (clade/lineage) occupied the island when it was connected with the other Gondwana landmasses in the Mesozoic. Causeways to Africa do not exist today, but have been proposed by some researchers for various times in the Cenozoic. Over-water dispersal could be from rafting on floating vegetation (flotsam) or by swimming/drifting. A recent appraisal of the geological data supported the idea of vicariance, but found nothing to justify the notion of past causeways. Here we review the biological evidence for the mechanisms that explain the origins of 28 of Madagascar's land vertebrate clades [two other lineages (the geckos Geckolepis and Paragehyra) could not be included in the analysis due to phylogenetic uncertainties]. The podocnemid turtles and typhlopoid snakes are conspicuous for they appear to have arisen through a deep-time vicariance event. The two options for the remaining 26 (16 reptile, five land-bound-mammal, and five amphibian), which arrived between the latest Cretaceous and the present, are dispersal across land bridges or over water. As these would produce very different temporal influx patterns, we assembled and analysed published arrival times for each of the groups. For all, a 'colonisation interval' was generated that was bracketed by its 'stem-old' and 'crown-young' tree-node ages; in two instances, the ranges were refined using palaeontological data. The synthesis of these intervals for all clades, which we term a colonisation profile, has a distinctive shape that can be compared, statistically, to various models, including those that assume the arrivals were focused in time. The analysis leads us to reject the various land bridge models (which would show temporal concentrations) and instead supports the idea of dispersal over water (temporally random). Therefore, the biological evidence is now in agreement with the geological evidence, as well as the filtered taxonomic composition of the fauna, in supporting over-water dispersal as the mechanism that explains all but two of Madagascar's land-vertebrate groups.

Downregulated miR-495-3p in colorectal cancer targets TGFßR1, TGFßR2, SMAD4 and BUB1 genes and induces cell cycle arrest.

BACKGROUND: Hsa-miR-495 (miR-495) has been extensively investigated in cancer initiation and progression. On the other hand, our bioinformatics analysis suggested that miR-495 exerts its effects through targeting of TGFß signaling components. METHODS & RESULTS: In order to investigate such an effect, miR-495 precursor was overexpressed in HEK293T, SW480, and HCT116 cells, which was followed by downregulation of TGFßR1, TGFßR2, SMAD4, and BUB1 putative target genes, detected by RT-qPCR. Also, luciferase assay supported the direct interaction of miR-495 with 3'UTR sequences of TGFßR1, TGFßR2, SMAD4, and BUB1 genes. Furthermore, a negative correlation of expression between miR-495-3p and some of these target genes was deduced in a set of colorectal and breast cancer cell lines. Then, flow cytometry analysis showed that the overexpression of miR-495 in HCT116 and HEK293T resulted in an arrest at the G1 phase. Consistently, western blotting analysis showed a significant reduction of the Cyclin D1 protein in the cells overexpressing miR-495, pointing to downregulation of the TGFß signaling pathway and cell cycle arrest. Finally, microarray data analysis showed that miR-495-3p is significantly downregulated in colorectal tumors, compared to the normal pairs. CONCLUSIONS: Overall, the results of the current study introduced miR-495-3p as a cell cycle progression suppressor, which may negatively regulate TGFßR1, TGFßR2, SMAD4, and BUB1 genes. This finding suggests miR-495-3p as a tumor suppressor candidate for further evaluation.

Comparative expression analysis of the Atoh7 gene regulatory network in the mouse and chicken auditory hindbrain.

The mammalian and avian auditory brainstem likely arose by independent evolution. To compare the underlying molecular mechanisms, we focused on Atoh7, as its expression pattern in the mammalian hindbrain is restricted to bushy cells in the ventral cochlear nucleus. We thereby took advantage of an Atoh7 centered gene regulatory network (GRN) in the retina including upstream regulators, Hes1 and Pax6, and downstream targets, Ebf3 and Eya2. In situ hybridization demonstrated for the latter four genes broad expression in all three murine cochlear nuclei at postnatal days (P) 4 and P30, contrasting the restricted expression of Atoh7. In chicken, all five transcription factors were expressed in all auditory hindbrain nuclei at embryonic day (E) 13 and P14. Notably, all five genes showed graded expression in the embryonic nucleus magnocellularis (NM). Atoh7 was highly expressed in caudally located neurons, whereas the other four transcription factors were highly expressed in rostrally located neurons. Thus, Atoh7 shows a strikingly different expression between the mammalian and avian auditory hindbrain. This together with the consistent absence of graded expression of GRN components in developing mammalian nuclei provide the first molecular support to the current view of convergent evolution as a major mechanism in the amniote auditory hindbrain. The graded expression of five transcription factors specifically in the developing NM confirms this nucleus as a central organizer of tonotopic features in birds. Finally, the expression of all five retinal GRN components in the auditory system suggests co-options of genes for development of sensory systems of distinct modalities.

Ancient DNA elucidates the lost world of western Indian Ocean giant tortoises and reveals a new extinct species from Madagascar.

Before humans arrived, giant tortoises occurred on many western Indian Ocean islands. We combined ancient DNA, phylogenetic, ancestral range, and molecular clock analyses with radiocarbon and paleogeographic evidence to decipher their diversity and biogeography. Using a mitogenomic time tree, we propose that the ancestor of the extinct Mascarene tortoises spread from Africa in the Eocene to now-sunken islands northeast of Madagascar. From these islands, the Mascarenes were repeatedly colonized. Another out-of-Africa dispersal (latest Eocene/Oligocene) produced on Madagascar giant, large, and small tortoise species. Two giant and one large species disappeared c. 1000 to 600 years ago, the latter described here as new to science using nuclear and mitochondrial DNA. From Madagascar, the Granitic Seychelles were colonized (Early Pliocene) and from there, repeatedly Aldabra (Late Pleistocene). The Granitic Seychelles populations were eradicated and later reintroduced from Aldabra. Our results underline that integrating ancient DNA data into a multi-evidence framework substantially enhances the knowledge of the past diversity of island faunas.

Lactate during ex-situ heart perfusion does not predict the requirement for mechanical circulatory support following donation after circulatory death (DCD) heart transplants.

BACKGROUND: Ex-situ heart perfusion (ESHP) is commonly used for the reanimation and preservation of hearts following donation after circulatory determined death (DCD). The only commercially available existing ESHP device promotes perfusate lactate levels for assessment of heart viability. The reliability of this marker is yet to be confirmed for DCD heart transplantation. METHODS: This is a single center, retrospective study examining DCD heart transplants from March 1, 2015 to June 30, 2020. Recipients were divided into 2 groups dependent upon their requirement for or absence of mechanical circulatory support post-transplant. Lactate profiles obtained during ESHP were analyzed. Hearts were procured using the direct procurement and perfusion (DPP) method. RESULTS: Fifty-one DCD heart transplant recipients were studied, of which 20 (39%) were dependent on mechanical circulatory support (MCS) following transplantation, (2% Ventricular Assist Device (VAD), 16% Extra Corporeal Membrane Oxygenation (ECMO) and 21% Intra-aortic balloon pumps (IABP). There was no difference in arterial lactate profiles on ESHP at any time point for those dependent upon MCS support (MCS) and those that were not (no MCS) post-transplant. After 3 hours of ESHP, the arterial lactate was >5mmol/L in 80% upon MCS vs 62% no MCS, p = .30. There was also no difference in ESHP rising arterial lactate concentrations, (15% MCS vs 13% non MCS, p = 1.00). CONCLUSION: For DCD hearts transplants retrieved using the DPP technique, lactate profiles do not seem to be a reliable predictor of mechanical circulatory support requirement post-transplant.

Acute aortic regurgitation due to fibrous strand rupture.

A 60-year-old male presented with sudden onset chest pain and pulmonary edema. The investigation confirmed torrential aortic regurgitation of a bicuspid valve. At surgery, a ruptured fibrous strand was identified which had been supporting the left-right cusp commissure with loss of attachment to the aortic wall. This case demonstrates that fibrous strands may be present as a supporting structure of the aortic valve, and rupture can be a rare cause of torrential aortic regurgitation, similar in pathogenesis to how it may be associated with acute severe mitral regurgitation and chordae tendineae rupture.

Pulmonary thromboendarterectomy-the Royal Papworth experience.

Background: Pulmonary thromboendarterectomy (PTE) was first introduced to the UK 25 years ago, and the UK national service is provided by a single hospital. The aim of this work is to summarize our experience and review activity and outcomes by era at a high-volume PTE center. During this period the understanding of chronic thromboembolic pulmonary hypertension (CTEPH) increased and drug treatments and balloon angioplasty were developed. We also review our contribution to the better understanding of this surgery and CTEPH. Methods: We retrospectively reviewed all patients undergoing PTE for CTEPH at our center between Jan 1997 and Sept 2019, dividing them into four equal cohorts. Pre-operative characteristics and post-operative outcomes are described by era. A MEDLINE search was performed and original scientific clinical publications from this unit were reviewed. Their contemporary relevance and influence to the evolution of the clinical service are discussed. Results: Over this 23-year period from the commencement of our program, 2,116 consecutive PTE were performed. The mean patient age was 57.8 years (range, 11-89 years). The first 25% of our PTE were performed over 12 years whilst the most recent 25% were performed in less than three years. Over time, the average pre-operative mean pulmonary artery pressure has not changed significantly. The 30-day mortality by era quartile has progressively fallen from 12.3% to 1.9% most recently (P<0.001). Overall, one year survival exceeded 90%. 17 publications influenced our practice development during this period. Conclusions: There was a consistent increase in activity and significant improvement in outcomes between the first and last quartiles of activity studied.

Early postoperative bleeding impacts long-term survival following first-time on-pump coronary artery bypass grafting.

BACKGROUND: Significant bleeding following cardiac surgery is a recognised complication, associated with a requirement for re-exploration and blood transfusion, both associated with increased morbidity and early mortality. The aim of this study was to examine the impact of the volume of early postoperative bleeding on long-term survival for patients undergoing coronary artery bypass grafting (CABG). METHODS: A retrospective analysis was performed of patients undergoing first-time isolated CABG at a single centre between January 2003 and April 2013, conditional from 30-day survival. RESULTS: Six thousand two hundred and sixty-five patients were analysed, with a mean Logistic EuroSCORE of 4.9%. The mean age was 67.8 years. Median follow-up was 11.5 years. The overall 10- and 15-year survival was 70.6% and 51.9% respectively. Following surgery, 4.6% (n=291) required return to theatre for re-exploration, and 43.6% (n=2,733) received at least one red cell transfusion. In multivariable analysis, the strongest correlates of mortality were age, smoking history, BMI, COPD, renal impairment, preoperative left ventricular function and preoperative haemoglobin (Hb) level. Twelve-hour blood loss was an additional predictor of inferior long-term survival. Five-year survival was 89.6% for patients with <500 mL blood loss, 86.8% for 500-1,000 mL and 83.8% for >1,000 mL. Re-exploration and receiving blood transfusion were not associated with reduced long-term survival. CONCLUSIONS: Significant 12-hour blood loss is associated with inferior long-term survival following CABG. This observation supports efforts aimed at improving intra-operative haemostasis and aggressive management of patients with early signs of bleeding.

Subxiphoid, Nonintubated, Opioid-Free, Video-Assisted Pneumonectomy: A New Frontier in Thoracic Surgery.

Surgical approaches to major pulmonary resections have evolved from thoracotomy to multiportal video-assisted thoracoscopy (VATS) and subsequently uniportal VATS. The efficacy of this progress has been validated in a multitude of publications demonstrating reductions in complications, patient perception of pain, and postoperative length of stay. More recent advances include subxiphoid extrathoracic access and nonintubated, opioid-free anesthesia. Early publications have demonstrated promising results with respect to safety, technical feasibility, and enhanced recovery. However, there remains a paucity of literature relating to hybrid approaches comprising both subxiphoid and nonintubated, opioid-free anesthesia in the context of pneumonectomy. The current report is the case of a patient undergoing pneumonectomy. Both subxiphoid and nonintubated, opioid-free techniques were utilized. The authors describe preoperative workup, surgical and anesthesia-related caveats, and postoperative recovery. In conclusion, this approach is technically feasible, safe, and may be associated with enhanced recovery.

Differential expression of microRNAs in the developing avian auditory hindbrain.

The avian auditory hindbrain is a longstanding model for studying neural circuit development. Information on gene regulatory network (GRN) components underlying this process, however, is scarce. Recently, the spatiotemporal expression of 12 microRNAs (miRNAs) was investigated in the mammalian auditory hindbrain. As a comparative study, we here investigated the spatiotemporal expression of the orthologous miRNAs during development of the chicken auditory hindbrain. All miRNAs were expressed both at E13, an immature stage, and P14, a mature stage of the auditory system. In most auditory nuclei, a homogeneous expression pattern was observed at both stages, like the mammalian system. An exception was the nucleus magnocellularis (NM). There, at E13, nine miRNAs showed a differential expression pattern along the cochleotopic axis with high expression at the rostromedial pole. One of them showed a gradient expression whereas eight showed a spatially selective expression at the rostral pole that reflected the different rhombomeric origins of this composite nucleus. The miRNA differential expression persisted in the NM to the mature stage, with the selective expression changed to linear gradients. Bioinformatics analysis predicted mRNA targets that are associated with neuronal developmental processes such as neurite and synapse organization, calcium and ephrin-Eph signaling, and neurotransmission. Overall, this first analysis of miRNAs in the chicken central auditory system reveals shared and strikingly distinct features between chicken and murine orthologues. The embryonic gradient expression of these GRN elements in the NM adds miRNA patterns to the list of cochleotopic and developmental gradients in the central auditory system.