Paediatric Renal Stone Management in Africa: A Scoping Review and Analysis of Current Practices.

Renal stones are solid deposits formed from minerals and salts that develop within the kidneys and urinary tract. While the condition is more common among adults, children and even infants can also be affected. There is an increasing incidence of paediatric renal stones in Africa alongside multiple challenges faced in managing the condition. This scoping review aimed to provide an overview of the management modalities of paediatric renal stones in Africa. This study utilised Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A systematic search was conducted in three electronic databases: PubMed, African Journal Online (AJOL), and Google Scholar, with 1,180 articles curated. After extensive examination, 10 articles satisfied the inclusion criteria. The review found that calcium oxalate stones were the most prevalent type, accounting for 34.03% of cases, followed by whewellite stones and ammonium urate stones. The most frequent location for stones was the kidney, and the most common symptom was pain. Abdominopelvic ultrasound was the most frequently utilised investigation. Of the 886 patients managed for renal stones, 75.4% were managed surgically, 2.9% medically, and 21.7% spontaneously resolved without intervention. This review identifies opportunities for improving the management of paediatric renal stones in Africa, including the need for standardised diagnostic and treatment protocols and the development of evidence-based guidelines tailored to the African context. Overall, this scoping review provides valuable insights into the patterns and management of paediatric renal stones in Africa and highlights the need for further research to improve the management of this condition in the region.

Optical-resolution photoacoustic microscopy with a needle-shaped beam.

Optical-resolution photoacoustic microscopy (OR-PAM) can visualize wavelength-dependent optical absorption at the cellular level. However, OR-PAM suffers from a limited depth of field (DOF) due to the tight focus of the optical excitation beam, making it challenging to acquire high-resolution images of samples with uneven surfaces or high-quality volumetric images without z-scanning. To overcome this limitation, we propose needle-shaped beam photoacoustic microscopy (NB-PAM), which can extend the DOF to up to ~28-fold Rayleigh lengths via customized diffractive optical elements (DOEs). The DOE generate a needle beam with a well-maintained beam diameter, a uniform axial intensity distribution, and negligible sidelobes. The advantage of using NB-PAM is demonstrated by both histology-like imaging of fresh slide-free organs using a 266 nm laser and in vivo mouse brain vasculature imaging using a 532 nm laser. The approach provides new perspectives for slide-free intraoperative pathological imaging and in-vivo organ-level imaging.

Structure, function, and evolution of metallo-ß-lactamases from the B3 subgroup-emerging targets to combat antibiotic resistance.

ß-Lactams are the most widely employed antibiotics in clinical settings due to their broad efficacy and low toxicity. However, since their first use in the 1940s, resistance to ß-lactams has proliferated to the point where multi-drug resistant organisms are now one of the greatest threats to global human health. Many bacteria use ß-lactamases to inactivate this class of antibiotics via hydrolysis. Although nucleophilic serine-ß-lactamases have long been clinically important, most broad-spectrum ß-lactamases employ one or two metal ions (likely Zn2+) in catalysis. To date, potent and clinically useful inhibitors of these metallo-ß-lactamases (MBLs) have not been available, exacerbating their negative impact on healthcare. MBLs are categorised into three subgroups: B1, B2, and B3 MBLs, depending on their sequence similarities, active site structures, interactions with metal ions, and substrate preferences. The majority of MBLs associated with the spread of antibiotic resistance belong to the B1 subgroup. Most characterized B3 MBLs have been discovered in environmental bacteria, but they are increasingly identified in clinical samples. B3-type MBLs display greater diversity in their active sites than other MBLs. Furthermore, at least one of the known B3-type MBLs is inhibited by the serine-ß-lactamase inhibitor clavulanic acid, an observation that may promote the design of derivatives active against a broader range of MBLs. In this Mini Review, recent advances in structure-function relationships of B3-type MBLs will be discussed, with a view to inspiring inhibitor development to combat the growing spread of ß-lactam resistance.

Single-shot 3D photoacoustic computed tomography with a densely packed array for transcranial functional imaging.

Photoacoustic computed tomography (PACT) is emerging as a new technique for functional brain imaging, primarily due to its capabilities in label-free hemodynamic imaging. Despite its potential, the transcranial application of PACT has encountered hurdles, such as acoustic attenuations and distortions by the skull and limited light penetration through the skull. To overcome these challenges, we have engineered a PACT system that features a densely packed hemispherical ultrasonic transducer array with 3072 channels, operating at a central frequency of 1 MHz. This system allows for single-shot 3D imaging at a rate equal to the laser repetition rate, such as 20 Hz. We have achieved a single-shot light penetration depth of approximately 9 cm in chicken breast tissue utilizing a 750 nm laser (withstanding 3295-fold light attenuation and still retaining an SNR of 74) and successfully performed transcranial imaging through an ex vivo human skull using a 1064 nm laser. Moreover, we have proven the capacity of our system to perform single-shot 3D PACT imaging in both tissue phantoms and human subjects. These results suggest that our PACT system is poised to unlock potential for real-time, in vivo transcranial functional imaging in humans.

VSIG4 interaction with heparan sulfates inhibits VSIG4-complement binding.

V-set and immunoglobulin domain-containing 4 (VSIG4) is a complement receptor of the immunoglobulin superfamily that is specifically expressed on tissue resident macrophages, and its many reported functions and binding partners suggest a complex role in immune function. VSIG4 is reported to have a role in immune surveillance as well as in modulating diverse disease phenotypes such as infections, autoimmune conditions, and cancer. However, the mechanism(s) governing VSIG4's complex, context-dependent role in immune regulation remains elusive. Here, we identify cell surface and soluble glycosaminoglycans, specifically heparan sulfates, as novel binding partners of VSIG4. We demonstrate that genetic deletion of heparan sulfate synthesis enzymes or cleavage of cell-surface heparan sulfates reduced VSIG4 binding to the cell surface. Furthermore, binding studies demonstrate that VSIG4 interacts directly with heparan sulfates, with a preference for highly sulfated moieties and longer glycosaminoglycan chains. To assess the impact on VSIG4 biology, we show that heparan sulfates compete with known VSIG4 binding partners C3b and iC3b. Furthermore, mutagenesis studies indicate that this competition occurs through overlapping binding epitopes for heparan sulfates and complement on VSIG4. Together these data suggest a novel role for heparan sulfates in VSIG4-dependent immune modulation.

A Scoping Review of Kidney Transplantation in Africa: How Far have We Come?

INTRODUCTION: Kidney transplantation is a life-saving treatment for end-stage kidney disease (ESKD) patients. However, access to this treatment in Africa lags behind other regions, leading to significant disparities in care. We aimed to analyse the indications, demographics, and outcomes of kidney transplantation in Africa. METHOD: We conducted a systematic review of studies from PubMed, Google Scholar, and African Journal Online using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We pooled and analysed data on procedure type, graft outcomes, donor type, prophylaxis, post-operative complications, and survival from 33 eligible studies. RESULT: The most common causes of ESKD requiring transplantation were glomerulonephritis and nephroangiosclerosis. Open nephrectomy was the predominant surgical approach (95%). Living donors accounted for 56.3% (4221) of all donors, with 68.5% being related to the recipient. Cadaveric donors accounted for 43.7% (3280) of transplants. Graft rejection was the most common surgical complication (39.44%), and 60.49% of patients developed hypertension in the follow-up period. CONCLUSION: Our study highlights the potential of kidney transplantation to improve the lives of ESKD patients in Africa. However, further research and infrastructure development are necessary to make this treatment more widespread and successful.

Single-shot optical projection tomography for high-speed volumetric imaging of dynamic biological samples.

A single-shot adaptation of Optical Projection Tomography (OPT) for high-speed volumetric snapshot imaging of dynamic mesoscopic biological samples is presented. Conventional OPT has been applied to in vivo imaging of animal models such as D. rerio, but the sequential acquisition of projection images typically requires samples to be immobilized during the acquisition. A proof-of-principle system capable of single-shot tomography of a ~1 mm3 volume is presented, demonstrating camera-limited rates of up to 62.5 volumes/s, which has been applied to 3D imaging of a freely swimming zebrafish embryo. This is achieved by recording eight projection views simultaneously on four low-cost CMOS cameras. With no stage required to rotate the sample, this single-shot OPT system can be implemented with a component cost of under £5000. The system design can be adapted to different sized fields of view and may be applied to a broad range of dynamic samples, including high throughput flow cytometry applied to model organisms and fluid dynamics studies.

Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy.

Obtaining frozen sections of bone tissue for intraoperative examination is challenging. To identify the bony edge of resection, orthopaedic oncologists therefore rely on pre-operative X-ray computed tomography or magnetic resonance imaging. However, these techniques do not allow for accurate diagnosis or for intraoperative confirmation of the tumour margins, and in bony sarcomas, they can lead to bone margins up to 10-fold wider (1,000-fold volumetrically) than necessary. Here, we show that real-time three-dimensional contour-scanning of tissue via ultraviolet photoacoustic microscopy in reflection mode can be used to intraoperatively evaluate undecalcified and decalcified thick bone specimens, without the need for tissue sectioning. We validate the technique with gold-standard haematoxylin-and-eosin histology images acquired via a traditional optical microscope, and also show that an unsupervised generative adversarial network can virtually stain the ultraviolet-photoacoustic-microscopy images, allowing pathologists to readily identify cancerous features. Label-free and slide-free histology via ultraviolet photoacoustic microscopy may allow for rapid diagnoses of bone-tissue pathologies and aid the intraoperative determination of tumour margins.

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion for the management of pediatric hydrocephalus in African centers - A systematic review and meta-analysis.

Background: Ventriculoperitoneal shunt (VPS) insertion and endoscopic third ventriculostomy (ETV) are common surgical procedures used to treat pediatric hydrocephalus. There have been numerous studies comparing ETV and VPS, but none from an African perspective. In this study, we sought to compare outcomes from African neurosurgical centers and review the associated complications. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in conducting this study. PubMed, Google Scholar, and African Journal Online were searched. Data on treatment successes and failures for ETV and VPS were pooled together and analyzed with a binary meta-analysis. A clinically successful outcome was defined as no significant event or complication occurring after surgery and during follow-up (e.g., infection, failure, CSF leak, malfunction, and mortality). Seven studies fully satisfied the eligibility criteria and were used in this review. Results: There was no statistically significant difference between the outcomes of ETV and VPS (OR- 0.27; 95% CI -0.39-0.94, P = 0.42). After reviewing the rates of complications of ETV and VPS from the identified studies, four were recurrent. The infection rates of ETV versus VPS were 0.02% versus 0.1%. The mortality rates were 0.01% versus 0.05%. The reoperation rates were 0.05% versus 0.3%, while the rates of ETV failure and shunt malfunction were 0.2% versus 0.2%. Conclusion: This study concludes that there is no significant difference between the outcomes of ETV and VPS insertion.

A Scoping Review of the Management of Benign Prostate Hyperplasia in Africa.

Benign prostatic hyperplasia (BPH) is a non-malignant prostate gland enlargement of unknown cause that affects more than 50% of men over 60 and is the most common cause of bladder outlet obstruction and voiding symptoms. BPH is treated primarily with watchful waiting, phytotherapy (herbs), and medical or surgical options. In this study, we sought to examine the different management practices in African urological centers, outcomes of management, and complications. A literature search was conducted using PubMed, African Journal Online, and Google Scholar regarding the management of BPH from inception till date. Articles were selected based on their relevance to the management of benign prostatic enlargement in Africa. Results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. The studies included were conducted from 1997 to 2022. They were from eight different African countries (Nigeria, Kenya, Togo, Ethiopia, Egypt, South Africa, Ghana, and Congo), with Nigeria contributing the most with 10 studies. Exactly 2999 patients were included in the study. Seventy-three (73.49%) percent of these patients totaling 2204, underwent surgical management of BPH, 124 (4.13%) patients were treated with phytomedicines or herbs, and 684 (22.80%) patients were treated with medical therapy. The complications and outcomes were studied and collated. A total of 808 patients opted for non-surgical treatment for BPH in the included studies. In this group, 124 were treated using phytochemicals or natural herbs, and 648 were treated with standard prescription medications. While surgical treatment for benign prostatic enlargement is shifting towards minimally invasive procedures in the developed world, open prostatectomy is still quite popular in Africa. Further research should focus not only on the reason for these disparities in management but also on the rationale for the selection of medical, surgical, or phytotherapy in African urological centres.

Long-Duration and Non-Invasive Photoacoustic Imaging of Multiple Anatomical Structures in a Live Mouse Using a Single Contrast Agent.

Long-duration in vivo simultaneous imaging of multiple anatomical structures is useful for understanding physiological aspects of diseases, informative for molecular optimization in preclinical models, and has potential applications in surgical settings to improve clinical outcomes. Previous studies involving simultaneous imaging of multiple anatomical structures, for example, blood and lymphatic vessels as well as peripheral nerves and sebaceous glands, have used genetically engineered mice, which require expensive and time-consuming methods. Here, an IgG4 isotype control antibody is labeled with a near-infrared dye and injected into a mouse ear to enable simultaneous visualization of blood and lymphatic vessels, peripheral nerves, and sebaceous glands for up to 3 h using photoacoustic microscopy. For multiple anatomical structure imaging, peripheral nerves and sebaceous glands are imaged inside the injected dye-labeled antibody mass while the lymphatic vessels are visualized outside the mass. The efficacy of the contrast agent to label and localize deep medial lymphatic vessels and lymph nodes using photoacoustic computed tomography is demonstrated. The capability of a single injectable contrast agent to image multiple structures for several hours will potentially improve preclinical therapeutic optimization, shorten discovery timelines, and enable clinical treatments.

Perceived helpfulness of alcohol protective behavioral strategies and consequence severity: A person-centered analysis.

Objective: College students report high rates of alcohol use and negative alcohol-related consequences (ARC). Many studies document that protective behavioral strategy (PBS) use is negatively associated with ARC. Few studies examine consequence severity and PBS helpfulness, both of which may provide nuance to this relationship. Participants and method: The current study used latent profile analysis to examine variability in PBS use, PBS helpfulness, ARC count, and ARC severity patterns among college students (n = 1156). We identified latent profiles and differences in alcohol use and drinking motives across profiles. Results: Three profiles best represented the data: (1) high PBS/low consequences, (2) moderate PBS/moderate consequences, (3) low PBS/high consequences. Conclusions: College students endorsing stronger drinking motives might be less likely to use and select helpful PBS and might experience more severe ARC. Results suggest that simple modifications to common measures can add depth of understanding and nuance to the examination of alcohol-related behaviors.

Interactions between 2'-fluoro-(carbamoylpyridinyl)deschloroepibatidine analogues and acetylcholine-binding protein inform on potent antagonist activity against nicotinic receptors.

Low-nanomolar binding constants were recorded for a series of six 2'-fluoro-(carbamoylpyridinyl)deschloroepibatidine analogues with acetylcholine-binding protein (AChBP). The crystal structures of three complexes with AChBP reveal details of molecular recognition in the orthosteric binding site and imply how the other three ligands bind. Comparisons exploiting AChBP as a surrogate for α4ß2 and α7 nicotinic acetylcholine receptors (nAChRs) suggest that the key interactions are conserved. The ligands interact with the same residues as the archetypal nAChR agonist nicotine yet display greater affinity, thereby rationalizing their in vivo activity as potent antagonists of nicotine-induced antinociception. An oxyanion-binding site is formed on the periphery of the AChBP orthosteric site by Lys42, Asp94, Glu170 and Glu210. These residues are highly conserved in the human α4, ß2 and α7 nAChR sequences. However, specific sequence differences are discussed that could contribute to nAChR subtype selectivity and in addition may represent a point of allosteric modulation. The ability to engage with this peripheral site may explain, in part, the function of a subset of ligands to act as agonists of α7 nAChR.

Assessing invariance of cannabis use motives by veteran status and binary gender identity among college students.

Student service members/veterans (SSM/V) are distinct from non-veteran students in a variety of ways, including in their cannabis use patterns and potentially their motives for cannabis use. Additionally, previous research has shown that men and women endorse different motives for their cannabis use. The present study was designed to assess whether a popular measure of cannabis use motives is invariant across veteran status and gender identity. Based on previous research, we hypothesized that cannabis motives would show invariance across SSM/V men, SSM/V women, non-veteran men, and non-veteran women (n = 1,011, SSM/V = 553) among those who indicated using cannabis at least once in their lifetime. Results from the four-group invariance testing procedure revealed metric invariance. This suggests that while the factor structure and factor loadings are invariant, there are differences at the intercept level for cannabis motives across groups. The same items load onto the same latent constructs and the strength of the items loading onto the latent factors was also the same across groups. The demonstrated invariance has implications for use in SSM/V and non-veteran clients. As this scale is brief, it could easily be used as a screening tool or used to guide intervention content.

Controllable Nonclassical Conductance Switching in Nanoscale Phase-Separated (PbI2 )1- x (BiI3 )x Layered Crystals.

Layered 2D (PbI2 )1- x (BiI3 )x materials exhibit a nonlinear dependence in structural and charge transport properties unanticipated from the combination of PbI2 and BiI3 . Within (PbI2 )1- x (BiI3 )x crystals, phase integration yields deceptive structural features, while phase boundary separation leads to new conductance switching behavior observed as large peaks in current during current-voltage (I-V) measurements (±100 V). Temperature- and time-dependent electrical measurements demonstrate that the behavior is attributed to ionic transport perpendicular to the layers. High-resolution transmission electron microscopy reveals that the structure of (PbI2 )1- x (BiI3 )x is a "brick wall" consisting of two phases, Pb-rich and Bi-rich. These brick-like features are 10s nm a side and it is posited that iodide ion transport at the interfaces of these regions is responsible for the conductance switching action.

Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning.

T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies.

Predicting a Need for Financial Assistance in Emergency Department Care.

Identifying patients with a low likelihood of paying their bill serves the needs of patients and providers alike: aligning government programs with their target beneficiaries while minimizing patient frustration and reducing waste among emergency physicians by streamlining the billing process. The goal of this study was to predict the likelihood of patients paying the balance of their emergency department visit bill within 90 days of receipt. Three machine learning methodologies were applied to predict payment: logistic regression, decision tree, and random forest. Models were trained and performance was measured using 1,055,941 patients with non-zero balances across 27 EDs from 1 August 2015 to 31 July 2017. The decision tree accurately predicted 87% of unsuccessful payments, providing significant opportunities to identify patients in need of financial assistance.

Are Smaller Emergency Departments More Prone to Volume Variability?

INTRODUCTION: Daily patient volume in emergency departments (ED) varies considerably between days and sites. Although studies have attempted to define "high-volume" days, no standard definition exists. Furthermore, it is not clear whether the frequency of high-volume days, by any definition, is related to the size of an ED. We aimed to determine the correlation between ED size and the frequency of high-volume days for various volume thresholds, and to develop a measure to identify high-volume days. METHODS: We queried retrospective patient arrival data including 1,682,374 patient visits from 32 EDs in 12 states between July 1, 2018-June 30, 2019 and developed linear regression models to determine the correlation between ED size and volume variability. In addition, we performed a regression analysis and applied the Pearson correlation test to investigate the significance of median daily volumes with respect to the percent of days that crossed four volume thresholds ranging from 5-20% (in 5% increments) greater than each site's median daily volume. RESULTS: We found a strong negative correlation between ED median daily volume and volume variability (R2 = 81.0%; P < 0.0001). In addition, the four regression models for the percent of days exceeding specified thresholds greater than their daily median volumes had R2 values of 49.4%, 61.2%, 70.0%, and 71.8%, respectively, all with P < 0.0001. CONCLUSION: We sought to determine whether smaller EDs experience high-volume days more frequently than larger EDs. We found that high-volume days, when defined as days with a count of arrivals at or above certain median-based thresholds, are significantly more likely to occur in lower-volume EDs than in higher-volume EDs. To the extent that EDs allocate resources and plan to staff based on median volumes, these results suggest that smaller EDs are more likely to experience unpredictable, volume-based staffing challenges and operational costs. Given the lack of a standard measure to define a high-volume day in an ED, we recommend 10% above the median daily volume as a metric, for its relevance, generalizability across a broad range of EDs, and computational simplicity.