Nephrology: What You May Have Missed in 2023.

This article highlights a selection of important nephrology studies published in 2023 that have relevance for nonnephrologist physicians. Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults.

The impact of nicotine smoking on spondyloarthritis and rheumatoid arthritis.

OBJECTIVE: Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such alteration can be a predisposing factor for autoimmune diseases such as spondyloarthritis (SpA) and rheumatoid arthritis (RA). This review aims to shed light on the effects of nicotine smoking on the pathophysiology, clinical presentation, and management of SpA and RA. METHODS: This review looked into the studies, excluding case reports and series, which were cited by PubMed/MEDLINE. RESULTS: Patients with established autoimmune conditions may have a different underlying pathophysiology and disease course when exposed to nicotine through cigarette smoking. Through the involvement of several cytokines, endothelial dysfunction, and epigenetic mechanisms, the severity of SpA is more prominent in smokers. The global health status, pain, and fatigue are worse in SpA patients. The evidence on the effect of nicotine smoking on the treatment of SpA is still limited. Nicotine can contribute to RA via the disruption of cellular regulatory activity, inflammatory responses, morphological, physiological, biochemical, and enzymatic responses. As such, smokers with RA have higher disease activity and are more likely to be seropositive through the citrullination of peptides. In addition, these patients are at risk of achieving a suboptimal response to tumor necrosis factor inhibitors. CONCLUSIONS: Cigarette smoking can substantially affect the pathophysiology and clinical presentation of patients with SpA and RA. The impact of nicotine on the management of these diseases still needs to be further studied.

Computer vision syndrome and dry eye symptoms among breastfeeding women.

INTRODUCTION: Breastfeeding women are susceptible to musculoskeletal symptoms and hormonal changes that can affect the ocular surface. As exposure to visual display units (VDU) that is known to cause symptoms of dry eye and computer vision syndrome (CVS) is increasing worldwide, including among breastfeeding women, it is unknown whether this group of VDU users would experience CVS more than non-breastfeeding women. Therefore, this study aimed to investigate the association between breastfeeding status and symptoms of CVS and dry eye. MATERIALS AND METHODS: In this cross-sectional study, selfreported CVS and dry eye symptoms were compared between 80 breastfeeding and 72 non-breastfeeding VDU users. Two questionnaires were administered online, which were the CVS-Questionnaire (CVS-Q) and the Ocular Surface Disease Index (OSDI) questionnaire, to evaluate symptoms of CVS and dry eye, respectively. Mann-Whitney test was used to compare CVS and OSDI scores between groups, while correlations between the scores were analyzed using Spearman's test. RESULT: Results showed that OSDI scores were significantly higher in the non-breastfeeding group (U = 2263, z-score = - 2.276, p = 0.023), indicating more dry eye symptoms experienced by respondents in this group, while no significant group difference was found in terms of CVS scores (U = 2772, z-score = -0.400, p = 0.689). Additionally, no significant association was observed between breastfeeding status and severity of dry eye symptoms as well as CVS symptoms. CONCLUSION: This study reported the possible benefit of breastfeeding in reducing dry eye symptoms. The CVS symptoms found in the breastfeeding group were possibly due to VDU usage rather than caused by breastfeeding. Public education on preventive measures to reduce the occurrence of CVS symptoms and ocular dryness among VDU users is essential to improve the quality of life.

Patterns and drivers of vector-borne microparasites in a classic metapopulation.

Many organisms live in fragmented populations, which has profound consequences on the dynamics of associated parasites. Metapopulation theory offers a canonical framework for predicting the effects of fragmentation on spatiotemporal host­parasite dynamics. However, empirical studies of parasites in classical metapopulations remain rare, particularly for vector-borne parasites. Here, we quantify spatiotemporal patterns and possible drivers of infection probability for several ectoparasites (fleas, Ixodes trianguliceps and Ixodes ricinus) and vector-borne microparasites (Babesia microti, Bartonella spp., Hepatozoon spp.) in a classically functioning metapopulation of water vole hosts. Results suggest that the relative importance of vector or host dynamics on microparasite infection probabilities is related to parasite life-histories. Bartonella, a microparasite with a fast life-history, was positively associated with both host and vector abundances at several spatial and temporal scales. In contrast, B. microti, a tick-borne parasite with a slow life-history, was only associated with vector dynamics. Further, we provide evidence that life-history shaped parasite dynamics, including occupancy and colonization rates, in the metapopulation. Lastly, our findings were consistent with the hypothesis that landscape connectivity was determined by distance-based dispersal of the focal hosts. We provide essential empirical evidence that contributes to the development of a comprehensive theory of metapopulation processes of vector-borne parasites.

Evaluation of a Capped Dosing Telavancin Regimen Compared to Standard Dosing at a Large Community Teaching Hospital.

Telavancin, a lipoglycopeptide antibiotic, is traditionally dosed at 10 mg/kg based on total body weight but is associated with toxicities that limit its use. This study supports the use of a capped dosing regimen of 750 mg in obese patients, which is associated with equal efficacy and fewer adverse effects compared to traditional dosing.

Designing of an epitope-based peptide vaccine against walking pneumonia: an immunoinformatics approach.

Mycoplasma pneumoniae is a substantial respiratory pathogen that develops not only pneumonia but also other respiratory diseases, which mimic viral respiratory syndromes. Nevertheless, vaccine development for this pathogen delays behind as immunity correlated with protection is now predominantly unknown. In the present study, an immunoinformatics pipeline is utilized for epitope-based peptide vaccine design, which can trigger a critical immune response against M. pneumoniae. A total of 105 T-cell epitopes from 12 membrane associated proteins and 7 T-cell epitopes from 5 cytadherence proteins of M. pneumoniae were obtained and validated. Thus, 18 peptides with 9-mer core sequence were identified as best T-cell epitopes by considering the number of residues with > 75% in favored region. Further, the crucial screening studies predicted three peptides with good binding affinity towards HLA molecules as best T-cell and B-cell epitopes. Based on this result, visualization, and dynamic simulation for the three epitopes (WIHGLILLF, VILLFLLLF, and LLAWMLVLF) were assessed. The predicted epitopes needs to be further validated for their adept use as vaccine. Collectively, the study opens up a new horizon with extensive therapeutic application against M. pneumoniae and its associated diseases.

Insights into pathological and molecular characterization of avipoxviruses circulating in Egypt.

1. Avipoxvirus (APV) infections are one of many threats inflicting economic losses within the poultry industry, particularly in tropical and subtropical countries. A proper and comprehensive study for APVs is needed to increase the knowledge concerning the diversity and evolution of the virus.2. For this purpose, 136 bird flocks of different species and breeding types were examined for APV infection between October 2016 and November 2017. One hundred and thirty samples had visible pocks on the chorioallantoic membrane (CAM) which were designated as fowl pox-like viruses via amplification of 578 bp from the P4b gene and 1800 bp from the fpv140 locus.4. A comprehensive phylogenetic analysis of fpv167 locus (P4b), fpv140 locus (fpv139 and fpv140) and fpv94 (DNA polymerase) revealed that all the analysed strains belong to fowl pox-like viruses (clade A; subclade A1 and A2). Based on the fpv140 locus full nucleotide sequence, three turkey originated strains were seen to be divergent from chicken originated sequences and branched into novel subclade A1.b.5. Trees comparison, within the term of speculation of virus-host specificity, clearly highlighted a high order specific subgrouping among subclades in the case of the fpv140 locus (including fpv139 and fpv140). Hence, the fowl poxvirus, turkey poxvirus and pigeon poxvirus strains clustered into distinct host-specific subclades A1a, A1.b and A2, respectively, which could not be seen in the FWPV-P4b and DNA polymerase phylogeny.

A New Tellurium- and Selenoorganic Compound as an Inhibitor of Acetylcholinesterase in Brain.

We studied the effect of a new cyanine dye containing selenium and tellurium on acetylcholinesterase activity in synaptic membrane in rat brain. The cyanine dye dose-dependently inhibits activity of this enzyme, and the concentration of half-maximal inhibition of acetylcholinesterase activity was 20.46 µM. The cyanine dye instantly inhibits the enzyme; the degree of inhibition depends on acetylthiocholine concentration: the lower is acetylthiocholine concentration, the higher is the degree of inhibition. On the Lineweaver-Burk plot, the concentration dependence curves of acetylcholinesterase with and without cyanine dye intersect in one point on the abscissa axis. In this case, the cyanine dye reduces the maximum inhibition rate (Vmax) and does not affect Michaelis constant (Km). The calculated inhibition constant Ki for the cyanine dye is 7.74 µM. Thus, the cyanine dye is a non-competitive inhibitor of acetylcholinesterase.

Hyperextension injuries of the knee: do patterns of bone bruising predict soft tissue injury?

OBJECTIVE: To establish whether patterns of soft tissue injury following knee hyperextension are associated with post-traumatic 'bone bruise' distribution. MATERIALS AND METHODS: Patients with a knee MRI within one year of hyperextension injury were identified at our institution over a 7 year period. MRIs, plain radiographs and clinical details of these patients were reviewed. RESULTS: Twenty-five patients were identified (median time from injury to MRI = 24 days). The most common sites of bone bruising were the anteromedial tibial plateau (48%) and anterolateral tibial plateau (44%). There were high rates of injury to the posterior capsule (52%), ACL (40%) and PCL (40%) but lower rates of injury to the menisci (20%), medial and lateral collateral ligaments (16%) and posterolateral corner (16%). Anterior tibial plateau oedema and rupture of the posterior capsule predicted cruciate ligament injury [OR = 10.5 (p = 0.02) and 24.0 (p = 0.001) respectively]. Whilst anterolateral tibial plateau oedema strongly predicted PCL injury [OR = 26.0, p = 0.003], ACL injury was associated with a variable pattern of bone bruising. Meniscal injury was unrelated to the extent or pattern of bone bruising. 5 out of 8 patients with a 'double sulcus' on the lateral radiograph had ACL injury. The presence of a double sulcus showed significant association with anteromedial kissing contusions (OR = 7.8, p = 0.03). CONCLUSIONS: Following knee hyperextension, bone bruising patterns may be associated with cruciate ligament injury. Other structures are injured less frequently and have weaker associations with bone bruise distribution. The double sulcus sign is a radiographic marker that confers a high probability of ACL injury.

Semi-automatic software based detection of atrial fibrillation in acute ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: Paroxysmal atrial fibrillation (PAF) is often asymptomatic and increases the risk of ischaemic stroke. Detection of PAF is challenging but crucial because a change of treatment decreases the risk of ischaemic stroke. Post-stroke investigations recommend at least 24-h continuous cardiac rhythm monitoring. Extended monitoring detects more PAF but is limited by costs due to manual analysis. Interpretive software might be a reasonable screening tool. The aim was to validate the performance and utility of Pathfinder SL software compared to manual analysis. METHODS: In all, 135 ischaemic stroke patients with no prior history of PAF or atrial fibrillation and who had done a 7-day continuous electrocardiogram monitoring (Holter) were included. Manual analysis was compared with Pathfinder SL software including a systematic control of registered events. RESULTS: Seventeen (12.6%) patients were diagnosed with PAF (atrial fibrillation > 30 s). Pathfinder SL software including a systematic control of events registered 16 (94.1%) patients with PAF. Manually 15 (88.2%) patients were detected with PAF. Pathfinder SL had a negative predictive value of 99% and sensitivity of 94%. CONCLUSIONS: Pathfinder SL software including a systematic evaluation of events is an acceptable alternative compared to manual analysis in PAF detection following ischaemic stroke. It is less time consuming and therefore a reliable, cheaper alternative compared to manual analysis.

Bioinspired dynamic microcapsules.

There is an increasing interest in bioinspired dynamic materials. Abundant illustrations of protein domains exist in nature, with remarkable ligand binding characteristics and structures that undergo conformational changes. For example, calmodulin (CaM) can have three conformational states, which are the unstructured Apo-state, Ca2+-bound ligand-exposed binding state, and compact ligand-bound state. CaM's mechanical response to biological cues is highly suitable for engineering dynamic materials. The distance between CaM globular terminals in the Ca2+-bound state is 5 nm and in the ligand-bound state is 1.5 nm. CaM's nanoscale conformational changes have been used to develop dynamic hydrogel microspheres that undergo reversible volume changes. The current work presents the fabrication and preliminary results of layer-by-layer (LbL) self-assembled Dynamic MicroCapsules (DynaMicCaps) whose multilayered shell walls are composed of polyelectrolytes and CaM. Quasi-dynamic perfusion results show that the DynaMicCaps undergo drastic volume changes, with up to ∼1500% increase, when exposed to a biochemical ligand trifluoperazine (TFP) at pH 6.3. Under similar test conditions, microcapsules without CaM also underwent volume changes, with only up to ∼290% increase, indicating that CaM's bio-responsiveness was retained within the shell walls of the DynaMicCaps. Furthermore, DynaMicCaps exposed to 0.1 M NaOH underwent volume changes, with only up to ∼580% volume increase. Therefore, DynaMicCaps represent a new class of polyelectrolyte multilayer (PEM) capsules that can potentially be used to release their payload at near physiological pH. With over 200 proteins that undergo marked, well-characterized conformational changes in response to specific biochemical triggers, several other versions of DynaMicCaps can potentially be developed.

Ovarian function after chemotherapy in young breast cancer survivors.

BACKGROUND: As cure rates for breast cancer improve, there is increasing evidence that late effects of treatment-and impaired fertility in particular-are emerging as important concerns among young breast cancer survivors. Older reports have evaluated the occurrence of amenorrhea after treatment, but few data have been reported about the incidence of biochemical evidence for impaired ovarian function in patients who do not become overtly menopausal. METHODS: We conducted a cross-sectional study evaluating anti-Müllerian hormone (amh) in premenopausal chemotherapy-treated breast cancer survivors and control patients. Random serum levels of amh and other relevant clinical data were collected for 100 premenopausal chemotherapy-treated breast cancer survivors and 76 control subjects. Subgroup analyses were performed for women with regular menstrual cycles at the time of amh testing. RESULTS: After adjustment for age, amh was significantly lower in the overall group of patients receiving chemotherapy (p = 0.002) and in the subgroup reporting normal cycles (p = 0.03). Cyclophosphamide produced a significant dose-dependent reduction in amh (p < 0.001); trastuzumab was associated with increased amh in survivors with normal cycles. Overall, serum amh in survivors was roughly equivalent to that measured in control patients 12 years older. CONCLUSIONS: Young breast cancer survivors often experience significant impairment of ovarian function despite having normal menstrual cycles after treatment. Those results have important implications for patient counselling and the timing of possible referral to a fertility specialist.

Genetic markers as therapeutic target in rheumatoid arthritis: A game changer in clinical therapy?

Rheumatoid arthritis (RA) is a chronic, inflammatory, multi-systemic autoimmune disease unremitted by genetic and environmental factors. The factors are crucial but inadequate in the development of disease; however, these factors can be representative of potential therapeutic targets and response to clinical therapy. Insights into the contribution of genetic risk factors are currently in progress with studies querying the genetic variation, their role in gene expression of coding and non-coding genes and other mechanisms of disease. In this review, we describe the significance of genetic markers architecture of RA through genome-wide association studies and meta-analysis studies. Further, it also reveals the mechanism of disease pathogenesis investigated through the mutual findings of functional and genetic studies of individual RA-associated genes, which includes HLA-DRB1, HLA-DQB1, HLA-DPB1, PADI4, PTPN22, TRAF1-C5, STAT4 and C5orf30. However, the genetic background of RA remains to be clearly depicted. Prospective efforts of the post-genomic and functional genomic period can travel toward real possible assessment of the genetic effect on RA. The discovery of novel genes associated with the disease can be appropriate in identifying potential biomarkers, which could assist in early diagnosis and aggressive treatment.

Metronomic chemotherapy and radiotherapy as salvage treatment in refractory or relapsed pediatric solid tumours.

BACKGROUND: Metronomic chemotherapy (mctx) combined with radiation therapy (rt) is an emerging anticancer strategy. The aim of the present study was to assess the efficacy of mctx combined with rt as salvage treatment in children with refractory or relapsed solid malignancies. METHODS: This prospective study enrolled patients with refractory or relapsed pediatric solid tumours from January 2013 to January 2015. Treatment consisted of 3-12 courses of mctx in all patients, followed by rt in patients who experienced local recurrence, distant metastases, or both. Each course of mctx consisted of oral celecoxib 100-400 mg twice daily (days 1-42), intravenous vinblastine 3 mg/m(2) weekly (weeks 1-6), oral cyclophosphamide 2.5 mg/m(2) daily (days 1-21), and oral methotrexate 15 mg/m(2) twice weekly (days 21-42). Statistical methods used were the log-rank test and binary logistic regression. RESULTS: A favourable disease response (partial response or stable disease) was seen in 49 of 64 patients (76.6%), with mild acute toxicity occurring in 41 (64%). After a median follow-up of 14 months, 1-year overall survival was 62%. Pattern of disease relapse (p < 0.0001), time from initial treatment to relapse (p = 0.0002), and response to treatment (p < 0.0001) significantly affected survival. Age was the only factor that significantly correlated with treatment toxicity (p = 0.002; hazard ratio: 3.37; 95% confidence interval: 1.53 to 7.35). CONCLUSIONS: Combining mctx with rt resulted in a favourable response rate, minimal toxicity, and 62% 1-year overall survival in patients with heavily pretreated recurrent disease. Patients with localized late recurrence or disease progression are the most likely to benefit from this regimen.

Photo-control of DNA binding by an engrailed homeodomain-photoactive yellow protein hybrid.

A photo-controlled version of the engrailed homeodomain (zENG) was created by inserting the homeodomain into a surface loop of a circularly permuted version of the photoactive yellow protein (cPYP). The two proteins fold independently as judged by NMR and fluorescence denaturation measurements. In the dark, the affinity of the zENG domain for its cognate DNA is inhibited >100-fold compared to wild-type zENG. Blue-light irradiation of the hybrid protein leads to enhanced conformational dynamics of the cPYP portion and a two-fold enhancement of the DNA binding affinity of the zENG domain. These results suggest that insertion into a surface loop of cPYP can be a general approach for conferring an initial level of photo-control on a given target protein. Focussed mutation/selection strategies may then be used to enhance the degree of photo-control.

Functional and prognostic relevance of -173 G/C gene polymorphism of macrophage migration inhibitory factor in sepsis patients in Egyptian intensive care units.

This study aimed to evaluate the association of plasma MIF level and -173 G/C single nucleotide polymorphism of the MIF gene with the occurrence, severity and mortality of sepsis patients. A study was conducted in adult surgical intensive care units of Zagazig University Hospitals, Egypt on 25 patients with sepsis, 27 with severe sepsis and 28 controls. Gram-negative bacilli were the most common isolates in both severe sepsis (63.0%) and sepsis (56.0%) patients. A highly statistically significant difference was found in MIF levels between sepsis cases and controls and a statistically significant difference as regards MIF level in different genotypes of the studied groups. MIF level was significantly associated with mortality in sepsis cases. High MIF levels and MIF -173G/C gene polymorphism are powerful predictors of the severity of sepsis and its outcome.

The use of robotics in surgery: a review.

IMPORTANCE: There is an ever-increasing drive to improve surgical patient outcomes. Given the benefits which robotics has bestowed upon a wide range of industries, from vehicle manufacturing to space exploration, robots have been highlighted by many as essential for continued improvements in surgery. OBJECTIVE: The goal of this review is to outline the history of robotic surgery, and detail the key studies which have investigated its effects on surgical outcomes. Issues of cost-effectiveness and patient acceptability will also be discussed. RESULTS AND CONCLUSION: Robotic surgery has been shown to shorten hospital stays, decrease complication rates and allow surgeons to perform finer tasks, when compared to the traditional laparoscopic and open approaches. These benefits, however, must be balanced against increased intraoperative times, vast financial costs and the increased training burden associated with robotic techniques. The outcome of such a cost-benefit analysis appears to vary depending on the procedure being conducted; indeed the strongest evidence in favour of its use comes from the fields of urology and gynaecology. It is hoped that with the large-scale, randomised, prospective clinical trials underway, and an ever-expanding research base, many of the outstanding questions surrounding robotic surgery will be answered in the near future.

Effect of butyrate, clopidol and their combination on the performance of broilers infected with Eimeria maxima.

1. The effect of butyric acid glycerides (BAGs) with and without clopidol (CLP) on Eimeria maxima on growth and associated biochemical variables was investigated in broiler chickens. 2. One-day-old chicks were divided into 6 equal groups (Gps) of 30 chicks each; each group was subdivided into 6 equal subgroups. Gp 1 was not infected and not treated. Chicks in Gp 2 were not infected and fed on a ration mixed with 4 g BAGs/kg for 6 successive weeks. Chicks of the other groups were directly inoculated intra-crop with 1 × 10(4) sporulated oocysts of E. maxima at 14 d of age. Gp 3 was infected and not treated. Chicks in the remaining three groups were given diets mixed with the tested drugs for 6 successive weeks. Gp 4 was fed on a diet mixed with CLP (125 g/kg). Gp 5 was given a diet mixed with BAGs (4 g/kg diet). Gp 6 was fed on a diet mixed with both BAGs (4 g/kg diet) and CLP (125 g/kg). 3. Birds in Gps 5 and 6 showed a reduction in the mean oocyst count, lesion scores and developmental stages in the lamina propria and improved growth and biochemical variables. BAG supplementation enhanced growth and production of healthy broilers. 4. It was concluded that BAGs were a useful supplement in broiler diets as an alternative to growth promoters and antimicrobial drugs.

Morphological and phenotypical characteristics of human osteoblasts after short-term space mission.

Morphological and phenotypical signs of cultured readaptation osteoblasts were studied after a short-term space mission. The ultrastructure and phenotype of human osteoblasts after Soyuz TMA-11 space flight (2007) were evaluated by scanning electron microscopy, laser confocal microscopy, and ELISA. The morphofunctional changes in cell cultures persisted after 12 passages. Osteoblasts retained the drastic changes in their shape and size, contour deformation, disorganization of the microtubular network, redistribution of organelles and specialized structures of the plasmalemma in comparison with the ground control cells. On the other hand, the expression of osteoprotegerin and osteocalcin (bone metabolism markers) increased; the expression of bone resorption markers ICAM-1 and IL-6 also increased, while the expression of VCAM-1 decreased. Hence, space flight led to the development of persistent shifts in cultured osteoblasts indicating injuries to the cytoskeleton and the phenotype changes, indicating modulation of bone metabolism biomarkers.

Construction of single-chain variable fragment antibodies against MCF-7 breast cancer cells.

A phage display library of single chain variable fragment (scFv) against MCF-7 breast cancer cells was constructed from C3A8 hybridoma cells. RNA from the C3A8 was isolated, cDNA was constructed, and variable heavy and light immunoglobulin chain gene region were amplified using PCR. The variable heavy and light chain gene regions were combined with flexible linker, linked to a pCANTAB 5E phagemid vector and electrophoresed into supE strain of Escherichia coli TG1 cells. Forty-eight clones demonstrated positive binding activity to MCF-7 breast cancer cell membrane fragments and the strongest of 48 clones was selected for analysis. The anti-MCF-7 library evaluated by SfiI and NotI digests demonstrated that anti-MCF-7 scFv antibodies possess individual patterns that should be able to recognize distinct human breast cancer cells. The C3A8 scFv, with an apparent molecular weight of 32 kDa, showed high homology (99%) with single chain antibody against rice stripe virus protein P20. In summary, the anti MCF-7 scFv antibody can be used for pretargeting breast cancer for clinical diagnosis of patients; it also has potential for therapeutic applications.