Circular Heterochiral Titanium-Based Self-Assembled Architectures.

Circular trinuclear helicates have been synthesized from a bis-biphenol strand (LH4), titanium isopropoxide, and various diimine ligands. These self-assembled architectures constructed around three TiO4N2 nodes have a heterochiral structure (C1 symmetry) when 2,2'-bipyridine (A), 4,4'-dimethyl-2,2'-bipyridine (B), 4,4'-bromo-2,2'-bipyridine (C), or 4,4'-dimethyl-2,2'-bipyrimidine (D) is employed. Within these complexes, one nitrogen ligand is endo-positioned inside the metallo-macrocycle, whereas the other two diimine ligands point outside the helicate framework. This investigation highlights that the nitrogen ligand which does not participate in the helicate framework of the complex controls the overall symmetry of the helicate since the 2,2'-bipyrimidine chelate (F) ends in the formation of a homochiral aggregate (C3 symmetry). The lack of symmetry found in the solid state for the trinuclear species ([Ti3L3(B)3], [Ti3L3(C)3], and [Ti3L3(D)3]) is observed for these complexes in solution (dichloromethane or chloroform). Remarkably, the 2,2'-bipyrazine ligand (ligand E) ends in the formation of a hexameric aggregate formulated as [Ti6L6(E)6], whereas the use of 4,4'-dimethyl-2,2'-bipyrimidine (ligand D) permits to generate the dinuclear complexes ([Ti2L(D)2(OiPr)4] and [Ti2L2(D)2]) in addition to the trimeric structure [Ti3L3(D)3]. The behavior of [Ti3L3(A)3] in solution, on the other hand, is unique since an equilibrium between the homochiral and the heterochiral form is reached within 17 days after the complex has been dissolved in dichloromethane (C3-[Ti3L3(A)3]/C1-[Ti3L3(A)3] ratio = 0.3). In chloroform, the heterochiral form of [Ti3L3(A)3] is stable for the same period of time, evidencing the dependence of this stereochemical transformation toward the solvent medium. The thermodynamic and kinetic parameters linked to this stereochemical equilibrium have been obtained and point to the fact that the transformation is intramolecular and not induced by the presence of external ligands. The thermodynamic constant of the C1-[Ti3L3(A)3]/C3-[Ti3L3(A)3] equilibrium is found to be K = 0.34 ± 10%. Further evidence to rationalize this solvent-induced symmetry switch is obtained via a DFT calculation and classical molecular dynamics. In particular, this computational investigation elucidates the reason why the stereochemical transformation of a heterochiral architecture into a homochiral structure is possible only for a trinuclear assembly containing ligand A.

A Chiral [2+3] Covalent Organic Cage Based on 1,1'-Bi-2-naphthol (BINOL) Units.

A [2+3] chiral covalent organic cage is produced through a dynamic covalent chemistry approach by mixing two readily available building units, viz. an enantiopure 3,3'-diformyl 2,2'-BINOL compound (A) with a triamino spacer (B). The two enantiomeric (R,R,R) and (S,S,S) forms of the cage C are formed nearly quantitatively thanks to the reversibility of the imine linkage. The X-ray diffraction analysis of cage (S,S,S)-C highlights that the six OH functions of the BINOL fragments are positioned inside the cage cavity. Upon reduction of the imine bonds of cage C, the amine cage D is obtained. The ability of the cage D to host the 1-phenylethylammonium cation (EH+) as a guest is evaluated through UV, CD and DOSY NMR studies. A higher binding constant for (R)-EH+ cation (Ka=1.7 106±10 % M-1) related to (S)-EH+ (Ka=0.9 106±10 % M-1) is determined in the presence of the (R,R,R)-D cage. This enantiopreference is in close agreement with molecular dynamics simulation.

Discovery and Visualization of the Hidden Relationships among N-Glycosylation, Disulfide Bonds, and Membrane Topology.

Membrane proteins (MPs) are functionally important but structurally complex. In particular, MPs often carry three structural features, i.e., transmembrane domains (TMs), disulfide bonds (SSs), and N-glycosylation (N-GLYCO). All three features have been intensively studied; however, how the three features potentially correlate has been less addressed in the literature. With the growing accuracy from computational prediction, we used publicly available information on SSs and N-GLYCO and analyzed the potential relationships among post-translational modifications (PTMs) and the predicted membrane topology in the human proteome. Our results suggested a very close relationship between SSs and N-GLYCO that behaved similarly, whereas a complementary relation between the TMs and the two PTMs was also revealed, in which the high SS and/or N-GLYCO presence is often accompanied by a low TM occurrence in a protein. Furthermore, the occurrence of SSs and N-GLYCO in a protein heavily relies on the protein length; however, TMs seem not to possess such length dependence. Finally, SSs exhibits larger potential dynamics than N-GLYCO, which is confined by the presence of sequons. The special classes of proteins possessing extreme or unique patterns of the three structural features are comprehensively identified, and their structural features and potential dynamics help to identify their susceptibility to different physiological and pathophysiological insults, which could help drug development and protein engineering.

Subclinical Myocardial Injury and the Phenotype of Clinical Congestion in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction.

BACKGROUND: Clinical congestion is associated with adverse outcomes in patients with heart failure. The pathophysiological mediators of this association remain uncertain. METHODS AND RESULTS: We prospectively enrolled a cohort of patients with heart failure and reduced left ventricular ejection fraction and performed a detailed clinical examination followed on the same day by an invasive right heart catheterization and blood sampling for biomarkers. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured. A clinical congestion score was calculated based on jugular venous pressure (cm H20 <10 = 0, 10-14 = 1, >14 = 2 points), bendopnea (0 vs 1), a third heart sound (0 vs 1), or peripheral edema (0-2). Congestion was categorized into tiers as absent (0 points), mild (1 point), or moderate to severe (≥ 2 points). We tested for associations of high-sensitivity troponin T, NT-proBNP, and elevated ventricular filling pressures with clinical congestion in both univariate and multivariable analyses. Of 153 participants, 65 (42%) had absent, 35 mild (23%), and 53 (35%) had moderate to severe clinical congestion. Congestion tier was associated with higher NT-proBNP and hs-troponin levels, and the right atrial pressure and pulmonary capillary wedge pressure (P < .001 for each). Increased congestion tier was also associated with the coexistent presence of elevated troponin T (≥52 ng/L), NT-proBNP (≥1000 pg/mL), and pulmonary capillary wedge pressure (≥22 mm Hg). Specifically, 78% of those with absent clinical congestion had 0 to 1 of these findings, whereas 75% of those with moderate-severe congestion had 2 or all 3 of these abnormalities (P < .001). An elevated hs-troponin was associated with mild or greater clinical congestion (odds ratio 3, 95% confidence interval 1.2-7.5, P = .02) in multivariable analysis adjusting for potential confounders including the right atrial pressure, pulmonary capillary wedge pressure, and NT-proBNP levels. CONCLUSIONS: Clinical congestion is a phenotype in which there is a high coexistent presence of elevated ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury. An elevated troponin was associated with clinical congestion in multivariable models that adjusted for ventricular filling pressures and natriuretic peptide levels. These data strengthen the evidence base for an association of elevated troponin with clinical congestion, suggesting that subclinical myocardial injury may be an important contributor to the pathophysiology of the congested state.

Shape-Sensing Robotic-Assisted Bronchoscopy with Concurrent use of Radial Endobronchial Ultrasound and Cone Beam Computed Tomography in the Evaluation of Pulmonary Lesions.

PURPOSE: Lung nodules are a common radiographic finding. Non-surgical biopsy is recommended in patients with moderate or high pretest probability for malignancy. Shape-sensing robotic-assisted bronchoscopy (ssRAB) combined with radial endobronchial ultrasound (r-EBUS) and cone beam computed tomography (CBCT) is a new approach to sample pulmonary lesions. Limited data are available regarding the diagnostic accuracy of combined ssRAB with r-EBUS and CBCT. METHODS: We conducted a retrospective analysis of the first 200 biopsy procedures of 209 lung lesions using ssRAB, r-EBUS, and CBCT at UT Southwestern Medical Center in Dallas, Texas. Outcomes were based on pathology interpretations of samples taken during ssRAB, clinical and radiographic follow-up, and/or additional sampling. RESULTS: The mean largest lesion dimension was 22.6 ± 13.3 mm with a median of 19 mm (range 7 to 73 mm). The prevalence of malignancy in our data was 64.1%. The diagnostic accuracy of ssRAB combined with advanced imaging was 91.4% (CI 86.7-94.8%). Sensitivity was 87.3% (CI 80.5-92.4%) with a specificity of 98.7% (CI 92.8-100%). The negative and positive predictive values were 81.3% and 99.2%. The rate of non-diagnostic sampling was 11% (23/209 samples). The only complication was pneumothorax in 1% (2/200 procedures), with 0.5% requiring a chest tube. CONCLUSION: Our results of the combined use of ssRAB with r-EBUS and CBCT to sample pulmonary lesions suggest a high diagnostic accuracy for malignant lesions with reasonably high sensitivity and negative predictive values. The procedure is safe with a low rate of complications.

Hidden Relationships between N-Glycosylation and Disulfide Bonds in Individual Proteins.

N-Glycosylation (NG) and disulfide bonds (DBs) are two prevalent co/post-translational modifications (PTMs) that are often conserved and coexist in membrane and secreted proteins involved in a large number of diseases. Both in the past and in recent times, the enzymes and chaperones regulating these PTMs have been constantly discovered to directly interact with each other or colocalize in the ER. However, beyond a few model proteins, how such cooperation affects N-glycan modification and disulfide bonding at selective sites in individual proteins is largely unknown. Here, we reviewed the literature to discover the current status in understanding the relationships between NG and DBs in individual proteins. Our results showed that more than 2700 human proteins carry both PTMs, and fewer than 2% of them have been investigated in the associations between NG and DBs. We summarized both these proteins with the reported relationships in the two PTMs and the tools used to discover the relationships. We hope that, by exposing this largely understudied field, more investigations can be encouraged to unveil the hidden relationships of NG and DBs in the majority of membranes and secreted proteins for pathophysiological understanding and biotherapeutic development.

Successful treatment of neurocysticercosis with albendazole desensitization.

BACKGROUND: Neurocysticercosis is a growing public health problem in the United States. Albendazole is a mainstay of medical therapy for neurocysticercosis, and here we present a case of hypersensitivity to albendazole leading to life-threatening disease progression. OBJECTIVE: To report the first successful albendazole desensitization protocol. METHODS: An oral albendazole 12-step desensitization protocol was developed, starting with 0.001 mg and progressing at 15 minutes intervals. Dosage for each subsequent step was as follows: 0.003 mg, 0.01 mg, 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300mg. RESULTS: The patient rapidly improved from a symptomatic standpoint, and repeat MRI showed a dramatic improvement in lesions. CONCLUSIONS: This successful desensitization protocol to albendazole can be of value to other patients with history suggestive of IgE-mediated allergy needing treatment for parasitic infections.

Single-Crystal X-ray Diffraction Studies of Solvated Crystals of C60 Reveal the Intermolecular Interactions between the Component Molecules.

The solid-state structures of seven solvates of C60 (C60·4tetrachloroethylene, C60·2tetrachloroethylene, C60·3benzene, C60· n-pentane, C60·diethyl ether, C60·chlorobenzene, and C60·benzene·dichloromethane) were determined by single-crystal X-ray diffraction at low temperature. At 90 K, the fullerene and solvate components are generally well-ordered and do not show the orientational disorder that plagues similar structures determined at room temperature. Interactions between the solvate molecules and the fullerene and between adjacent C60 molecules were examined and analyzed. Van der Waals and weak charge-transfer interactions are important to help to organize the individual components in these structures. The weak Lewis acid behavior of C60, such as when it cocrystallizes with diethyl ether or chlorinated solvents, is apparent. In addition, π-stacking interactions are prevalent. The solvates of C60 reported here were frequently obtained from attempts to cocrystallize C60 with another chemical compound. Although the desired cocrystals were never formed, the unincorporated molecules influenced solvate formation.

Selective activation of p53-mediated tumour suppression in high-grade tumours.

Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related death worldwide, with an overall 5-year survival rate of only 10-15%. Deregulation of the Ras pathway is a frequent hallmark of NSCLC, often through mutations that directly activate Kras. p53 is also frequently inactivated in NSCLC and, because oncogenic Ras can be a potent trigger of p53 (ref. 3), it seems likely that oncogenic Ras signalling has a major and persistent role in driving the selection against p53. Hence, pharmacological restoration of p53 is an appealing therapeutic strategy for treating this disease. Here we model the probable therapeutic impact of p53 restoration in a spontaneously evolving mouse model of NSCLC initiated by sporadic oncogenic activation of endogenous Kras. Surprisingly, p53 restoration failed to induce significant regression of established tumours, although it did result in a significant decrease in the relative proportion of high-grade tumours. This is due to selective activation of p53 only in the more aggressive tumour cells within each tumour. Such selective activation of p53 correlates with marked upregulation in Ras signal intensity and induction of the oncogenic signalling sensor p19(ARF)( )(ref. 6). Our data indicate that p53-mediated tumour suppression is triggered only when oncogenic Ras signal flux exceeds a critical threshold. Importantly, the failure of low-level oncogenic Kras to engage p53 reveals inherent limits in the capacity of p53 to restrain early tumour evolution and in the efficacy of therapeutic p53 restoration to eradicate cancers.

Selectivity Enhancement by Using Double-Layer MOX-Based Gas Sensors Prepared by Flame Spray Pyrolysis (FSP).

Here we present a novel concept for the selective recognition of different target gases with a multilayer semiconducting metal oxide (SMOX)-based sensor device. Direct current (DC) electrical resistance measurements were performed during exposure to CO and ethanol as single gases and mixtures of highly porous metal oxide double- and single-layer sensors obtained by flame spray pyrolysis. The results show that the calculated resistance ratios of the single- and double-layer sensors are a good indicator for the presence of specific gases in the atmosphere, and can constitute some building blocks for the development of chemical logic devices. Due to the inherent lack of selectivity of SMOX-based gas sensors, such devices could be especially relevant for domestic applications.

Endoscopic submucosal dissection training with ex vivo human gastric remnants.

BACKGROUND: Endoscopic submucosal dissection (ESD) offers en bloc resection of early cancer or precancerous lesions, potentially saving patients from major organ resection, such as gastrectomy, colectomy, and esophagectomy. Japan now leads the world in ESD due to its high rate of gastric cancer. Western countries, with their lower gastric cancer rates, do not get as much experience with the technique. Training in ESD utilizing both in vivo and ex vivo porcine stomach has been shown to decrease rates of perforation and operative time. Both models can be prohibitively expensive or not generally available to the majority of endoscopists on a regular basis. This study describes the framework for using human gastric remnants from sleeve gastrectomy patients for ESD training. METHODS: Patients undergoing sleeve gastrectomy for morbid obesity were consented for use of their gastric specimen before surgery. The specimen was weighed and measured by the pathologist and then used for ESD training. The specimen was mounted to a 15-mm laparoscopic port and secured using a pursestring suture. ESD was then performed through this port. RESULTS: We were able to successfully use this model to resect multiple marked out lesions in an en bloc fashion. Training using this model has improved our dissection times from approximately 2 h to 30 min for a 2-cm simulated lesion. CONCLUSIONS: ESD requires the endoscopist to perform a surgical dissection. Until now, development of these skills required intensive training on porcine models that are not widely available. We were able to create a method using the excised portion from sleeve gastrectomy patients, providing a more accessible and cost-effective model for ESD training and potentially other endoscopic therapeutic modalities.

Robotic-assisted Bronchoscopy Combined with Multimodal Imaging for Targeted Lung Cryobiopsies.

Robotic-assisted bronchoscopy (RAB) allows for targeted bronchoscopic biopsy in the lung. A robotic-assisted bronchoscope is navigated through the airways under direct vision after establishing a pathway to a target lesion based on mapping performed on a 3-dimensional (3D) lung and airway reconstruction obtained from a pre-procedure thin-slice computed tomography chest. RAB has maneuverability to distal airways throughout the lung, precise catheter tip articulation, and stability with the robotic arm. Adjunct imaging tools such as fluoroscopy, radial endobronchial ultrasound (r-EBUS), and cone beam computed tomography (CBCT) can be used with RAB. Studies using shape-sensing robotic-assisted bronchoscopy (ssRAB) have shown favorable diagnostic outcomes and safety profiles in both malignant and non-malignant processes for the biopsy of peripheral pulmonary lesions (PPLs). A 1.1 mm cryoprobe combined with ssRAB has been shown to be safe and effective for the diagnosis of PPLs compared to a traditional bronchoscopy with forceps biopsy. This technique can also be used for targeted lung sampling in benign processes. The aim of this article is to describe a stepwise approach to performing RAB combined with fluoroscopy, r-EBUS, and CBCT to obtain targeted transbronchial lung cryobiopsies (TBLC).

A review of CONCEPTT study findings including subanalyses in pregnant women using continuous glucose monitoring with type 1 diabetes and their offspring.

The main objective of this article is to provide a comprehensive review of continuous glucose monitor (CGM) use in pregnant women with type 1 diabetes (T1D) from the CONCEPTT study including subanalyses. Literature search was accessed through MEDLINE (1966-September 2023) using the key terms: CONCEPTT, pregnancy, women, T1D, and CGM with limitations set to distinguish human subjects written in English. A total of 17 publications including one main clinical trial and 15 subanalyses have been published to date regarding the use of CGM in pregnant women with T1D which were conducted by a research group identified as the CONCEPTT Collaborative Group. While advances in maternal care have resulted in safer pregnancy for both the mother and child, women with preexisting T1D and pregnancy still experience higher rates of complications both in the short and long term. The use of CGM in pregnancy has not been studied extensively until more recently. The CONCEPTT clinical trial was a landmark study that involved several subanalyses. The main trial proved that CGM use in T1D pregnancy resulted in less hyperglycemia in the third trimester, reduced large for gestational age (LGA, >90th percentile), reduced neonatal intensive care unit admissions lasting longer than 24 h, and reduced neonatal hypoglycemia. Although subanalyses showed a variety of results including 'inconclusive' due to lack of prespecification, it is believed that CGM in T1D during pregnancy is to be recommended and used for overall improved outcomes.

Narrative review of data supporting alternate first-line therapies over metformin in type 2 diabetes.

Purpose: Metformin has been the first-line treatment for type 2 diabetes mellitus as monotherapy or concomitantly with other glucose-lowering therapies due to its efficacy, safety, and affordability. Recent studies on the cardioprotective and renoprotective benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have influenced guidelines on diabetes management to consider these newer agents as alternative first-line therapies. This paper explores the literature supporting the use of these newer medications alone as a first-line agent in place of metformin. Methods: A review of citations from the most recent guidelines along with a literature search via PubMed was completed to review (1) what, historically, made metformin first-line (2) if newer agents' benefits remain when used without metformin (3) how newer agents compare against metformin when used without it. Results: Evaluation of the historical literature was completed to summarize the key findings that support metformin as a first-line therapy agent. Additionally, an assessment of the literature reveals that the benefits of these two newer classes are independent of concomitant metformin therapy. Finally, studies have demonstrated that these newer agents can be either non-inferior or sometimes superior to metformin when used as monotherapy. Conclusion: GLP-1 RA and SGLT-2i can be considered as first line monotherapies for select patients with high cardiovascular risks, renal disease, or weight loss requirements. However, pharmacoeconomic considerations along with lesser long-term safety outcomes should limit these agents' use in certain patients as the management of diabetes continues to transition towards shared-decision making. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01406-6.

Molecular Diagnostics for Invasive Fungal Diseases: Current and Future Approaches.

Invasive fungal diseases (IFDs) comprise a growing healthcare burden, especially given the expanding population of immunocompromised hosts. Early diagnosis of IFDs is required to optimise therapy with antifungals, especially in the setting of rising rates of antifungal resistance. Molecular techniques including nucleic acid amplification tests and whole genome sequencing have potential to offer utility in overcoming limitations with traditional phenotypic testing. However, standardisation of methodology and interpretations of these assays is an ongoing undertaking. The utility of targeted Aspergillus detection has been well-defined, with progress in investigations into the role of targeted assays for Candida, Pneumocystis, Cryptococcus, the Mucorales and endemic mycoses. Likewise, whilst broad-range polymerase chain reaction assays have been in use for some time, pathology stewardship and optimising diagnostic yield is a continuing exercise. As costs decrease, there is also now increased access and experience with whole genome sequencing, including metagenomic sequencing, which offers unparalleled resolution especially in the investigations of potential outbreaks. However, their role in routine diagnostic use remains uncommon and standardisation of techniques and workflow are required for wider implementation.

Catheterization Without Supination-A Series of 36 Prone Position Internal Jugular Vein Cannulations.

Describe the clinical characteristics and outcomes of 32 critically ill patients who underwent central venous cannulation of the internal jugular vein while in prone position. DESIGN: Retrospective cohort analysis. SETTING: Single tertiary-care urban academic safety-net hospital. PATIENTS/SUBJECTS: Patients requiring mechanical ventilation and prone positioning for severe acute respiratory distress syndrome from March 1, 2020, through March 31, 2021. INTERVENTIONS: Internal jugular vein cannulation while in the prone position. MEASUREMENTS AND MAIN RESULTS: The technique used for venous access, procedural complications, patient demographics, and clinical outcomes are described. Thirty-six prone internal jugular vein cannulations for 32 hemodialysis catheters and four central venous catheters were successfully performed in 32 patients. One immediate and one delayed pneumothorax occurred. Inhospital mortality was 88%. CONCLUSIONS: In the largest series to date, cannulation of the internal jugular vein with the patient in prone position is feasible but associated with a 6% risk of pneumothorax. Severity of illness in patients intolerant of supine positioning results in high inhospital mortality.

Radiation dose of cone beam CT combined with shape sensing robotic assisted bronchoscopy for the evaluation of pulmonary lesions: an observational single center study.

Background: Shape sensing robotic-assisted bronchoscopy (ssRAB) combined with radial endobronchial ultrasound (r-EBUS) and cone beam computed tomography (CBCT) is a newer diagnostic modality for the evaluation of pulmonary lesions. There is limited data describing the radiation dose of CBCT combined with ssRAB. The purpose of this study was to describe the technical factors associated with the use of CBCT combined with ssRAB to biopsy pulmonary lesions. Methods: We conducted a single center, prospective observational study of patients undergoing ssRAB combined with fixed CBCT for the pulmonary lesion biopsy. We report our patient demographics, and pulmonary lesion and procedure characteristics. Results: A total of 241 ssRAB procedures were performed to biopsy 269 pulmonary lesions. The mean lesion size was measured in the following dimensions: anteroposterior (18.0±8.8 mm), transverse (17.2±10.5 mm), and craniocaudal (17.7±10.2 mm). A mean of 1.5±0.7 (median: 1, range: 1-4) CBCT spins were performed. The mean total fluoroscopy time (FT) was 5.6±2.9 minutes. The mean radiation dose of cumulative air kerma (CAK) was 63.5±46.7 mGy and the mean cumulative dose area product (DAP) was 22.6±16.0 Gy·cm2. Diagnostic yield calculated based on results at index bronchoscopy was 85.9%. There was a low rate of complications with 8 pneumothoraces (3.3%), 5 (2.1%) of which required chest tube placement. Conclusions: We describe the use of ssRAB combined with CBCT to biopsy pulmonary lesions as a safe diagnostic modality with relatively low radiation dose that is potentially comparable to other image guided sampling modalities. Bronchoscopists should be cognizant of the radiation use during the procedure for both patient and staff safety.

Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections.

Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.

Arthropod-Borne Flaviviruses in Pregnancy.

Flaviviruses are a diverse group of enveloped RNA viruses that cause significant clinical manifestations in the pregnancy and postpartum periods. This review highlights the epidemiology, pathophysiology, clinical features, diagnosis, and prevention of the key arthropod-borne flaviviruses of concern in pregnancy and the neonatal period-Zika, Dengue, Japanese encephalitis, West Nile, and Yellow fever viruses. Increased disease severity during pregnancy, risk of congenital malformations, and manifestations of postnatal infection vary widely amongst this virus family and may be quite marked. Laboratory confirmation of infection is complex, especially due to the reliance on serology for which flavivirus cross-reactivity challenges diagnostic specificity. As such, a thorough clinical history including relevant geographic exposures and prior vaccinations is paramount for accurate diagnosis. Novel vaccines are eagerly anticipated to ameliorate the impact of these flaviviruses, particularly neuroinvasive disease manifestations and congenital infection, with consideration of vaccine safety in pregnant women and children pivotal. Moving forward, the geographical spread of flaviviruses, as for other zoonoses, will be heavily influenced by climate change due to the potential expansion of vector and reservoir host habitats. Ongoing 'One Health' engagement across the human-animal-environment interface is critical to detect and responding to emergent flavivirus epidemics.