Recycling transplanted organs: An exceptional case and literature review.

BACKGROUND: Recycling transplant kidneys, in other words using an allograft which has previously been transplanted in one recipient for transplant in a second recipient, can be a source of opportunity for expanding the pool of available grafts in the United States and beyond. SUMMARY: We describe a case of renal transplantation from a donor who had undergone a kidney transplant 3 years prior and had good graft function at the time of procurement. The recipient underwent transplantation uneventfully and to date has demonstrated excellent graft function. We also include a literature review of reported cases of recycled/retransplanted kidneys. KEY MESSAGES: -Recycling transplanted kidneys is a largely untapped resource which could help decrease the transplant waitlist. -Utilizing such kidneys does need special considerations in terms of procurement technique, backtable, crossmatch, recipient selection and follow-up.

Impact of the Order of Movement on the Median Nerve Root Function: A Neurophysiological Study with Implications for Neurodynamic Exercise Sequencing.

Background: Neurodynamic exercise is a common clinical practice used to restore neural dynamic balance. The order in which movements are performed during these exercises is believed to play a crucial role in their effectiveness. This study aimed to investigate the impact of different sequences of neurodynamic exercise on nerve root function, with a specific focus on the median nerve. Methods: Participants were assigned randomly to three experimental groups, each undergoing a different test sequence: standard, proximal-to-distal, and distal-to-proximal. Dermatomal somatosensory evoked potentials (DSSEPs) were recorded at key levels (C6, C7, C8, and T1). Results: The findings revealed a significant influence of the movement sequence on DSSEP amplitudes. The execution of neurodynamic exercise in the proximal-to-distal sequence was associated with a notable reduction in amplitudes (p < 0.05). Conversely, the distal-to-proximal sequence resulted in increased amplitudes compared to the standard sequence (p < 0.05). Conclusions: This study underscores the importance of carefully considering the order of movements during neurodynamic exercising, particularly when evaluating nerve roots that lack the protective perineurium. The choice of sequence appears to have a substantial impact on nerve function, with implications for optimizing clinical neurodynamic exercise techniques.

Concomitant Polyoma BK Virus and West Nile Virus in Renal Allografts.

Surveillance of the renal allograft recipient is essential when monitoring renal function to detect the early onset of rejection and alter therapeutic treatments to treat acute rejection or other causes and improve long-term graft function. If renal function begins to deteriorate, a renal biopsy is often indicated to assess the Banff grade of potential rejection or other causes, especially in the setting of polyoma BK viral load elevation. Although BK infection in the allograft is asymptomatic, reactivation of the virus is known to be associated with the acceleration of pathologic change and a poor outcome in the allograft. BK reactivation in a transplant kidney is not uncommon, and determining inflammation related to the virus versus acute rejection is paramount for appropriate immunosuppressive therapy management. We identified a concomitant polyoma BK virus and West Nile Virus (WNV) infection in two renal transplant patients which, to our knowledge, has not previously been reported. However, other concomitant infections have been reported in renal allografts including BK virus and cytomegalovirus (CMV), CMV and hepatitis C (HCV), and HCV and human immunodeficiency virus (HIV). As WNV has become endemic in many regions of the United States, and since the transmission of the virus via transplanted organs is associated with significant morbidity and mortality, it may be prudent to consider serologic screening for WNV in living donors prior to organ procurement. Regardless, the observation we made and report here should underscore the potential for concomitant viral infections that may be masked when a renal allograft has a significant inflammatory response to BK virus.

BRCA1 and BRCA2 deficient tumour models generate distinct ovarian tumour microenvironments and differential responses to therapy.

Clinical trials are currently exploring combinations of PARP inhibitors and immunotherapies for the treatment of ovarian cancer, but their effects on the ovarian tumour microenvironment (TME) remain unclear. Here, we investigate how olaparib, PD-L1 monoclonal antibodies, and their combination can influence TME composition and survival of tumour-bearing mice. We further explored how BRCA deficiencies can influence the response to therapy. Olaparib and combination therapies similarly improved the median survival of Brca1- and Brca2-deficient tumour-bearing mice. Anti-PD-L1 monotherapy improved the survival of mice with Brca1-null tumours, but not Brca2-null tumours. A detailed analysis of the TME revealed that olaparib monotherapy resulted in a large number of immunosuppressive and immunomodulatory effects in the more inflamed Brca1-deficient TME but not Brca2-deficient tumours. Anti-PD-L1 treatment was mostly immunosuppressive, resulting in a systemic reduction of cytokines and a compensatory increase in PD-L1 expression. The results of the combination therapy generally resembled the effects of one or both of the monotherapies, along with unique changes observed in certain immune populations. In-silico analysis of RNA-seq data also revealed numerous differences between Brca-deficient tumour models, such as the expression of genes involved in inflammation, angiogenesis and PD-L1 expression. In summary, these findings shed light on the influence of novel therapeutics and BRCA mutations on the ovarian TME.

Drug policies' sensitivity towards women, pregnancy, and motherhood: a content analysis of national policy and programs from nine countries and their adherence to international guidelines.

BACKGROUND AND OBJECTIVES: Substance use in women is associated with unique psycho-social and physical vulnerabilities and poses complex challenges during pregnancy and motherhood. Gender-sensitive drug policy which considers the needs of women and their children could address these concerns. The objectives of this study were: (1) to systematically explore national-level drug policies' sensitivity and responsiveness to women, pregnant women, and children; and (2) to examine the adherence of drug policies with international guidelines for gender sensitivity in drug policy. METHODS: The research team was diverse professional backgrounds and nine countries. A summative content analysis of national drug policy documents, action plans, and strategies was performed. Specific documents focusing on women, pregnancy, and children were analysed. Specific themes and how frequently they appeared in the documents were identified. This quantification was an attempt to explore usage indicating the relative focus of the policies. A thematic map was developed to understand how national-level drug policies conceive and address specific concerns related to women who use drugs. We adapted the UNODC checklist for gender mainstreaming to assess policies' adherence to international guidelines. RESULTS: Twenty published documents from nine countries were reviewed. The common themes that emerged for women, pregnancy, and children were needs assessment, prevention, treatment, training, supply reduction, and collaboration and coordination. Custody of children was a unique theme for pregnant women. Specific psycho-social concerns and social reintegration were special themes for women, whereas legislation, harm reduction, research, and resource allocation were children-specific additional themes. For women-specific content analysis, special issues/concerns in women with drug misuse, need assessment, and prevention were the three most frequent themes; for the children-specific policies, prevention, training, and treatment comprised the three most occurring themes. For pregnant women/pregnancy, prevention, treatment, and child custody were the highest occurring themes. According to ratings of the countries' policies, there is limited adherence to international guidelines which ensure activities are in sync with the specific needs of women, pregnant women and their children. CONCLUSION: Our analysis should help policymakers revise, update and adapt national policies to ensure they are gender-responsive and address the needs of women, pregnant women and their children.

Correlation of Red Blood Cell Casts With Renal Dysfunction in Patients With Infection-related Glomerulonephritis.

CONTEXT.­: Infection-related glomerulonephritis (IRGN) usually manifests as a proliferative immune-complex glomerulonephritis. The degree of renal dysfunction at presentation can vary. Association with histologic features on kidney biopsy remains unknown. OBJECTIVE.­: To study the correlation between renal function in IRGN at the time of biopsy and the severity of histologic features. DESIGN.­: Culture-proven IRGN cases at our facility were included and divided based on estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m2. Patients' demographic and pathologic findings were obtained from electronic medical records and kidney biopsy reports. RESULTS.­: In total, 104 cases were diagnosed with IRGN on biopsy (mean age, 55.6 ± 15.6 years; male, n = 79 [76%]; median eGFR, 14.5 mL/min/1.73 m2), and 51 of 104 showed eGFR <15 mL/min/1.73 m2. Among all the histologic features assessed, only percent tubules with red blood cell (RBC) casts showed statistical difference, being significantly higher in the lower eGFR group (P = .004). Multivariable logistic regression analysis also showed that %tubules with RBC casts were associated with lower eGFR (odds ratio, 1.12; 95% CI, 1.01-1.24; P = .01). Patients with 5% or more RBC casts (n = 31) showed a lower eGFR (P = .02) and a higher %cellular crescent (P < .001) compared with those with less than 5% RBC casts. Patients with concomitant anticoagulant therapy (n = 11) showed higher percentages of RBC casts than those without anticoagulants (P = .02). CONCLUSIONS.­: Particular attention to the extent of RBC casts on kidney biopsy is recommended in patients with IRGN because these portend worse renal dysfunction, more so in patients requiring anticoagulation (including for hemodialysis) because they are especially vulnerable to developing anticoagulant-related nephropathy.

Plasma Wnt7b protein in rheumatoid arthritis: Detection of interstitial lung disease.

OBJECTIVE: To determine the plasma level of Wingless-related integration site 7b (Wnt7b) protein in rheumatoid arthritis (RA) patients (with and without interstitial lung disease (ILD)) and in idiopathic pulmonary fibrosis (IPF) patients and its relationship with RA disease activity and/or severity of pulmonary fibrosis. To assess the validity of plasma Wnt7b for the detection of ILD among RA patients. METHOD: This case-control study included 128 subjects (32 RA-ILD, 32 RA, 32 IPF, and 32 healthy controls). RA and RA-ILD Patients were evaluated for disease activity by DAS28 and disease activity grades were recorded according to DAS28 grades. Laboratory parameters as Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF), Anti-citrullinated peptide (Anti-CCP) were recorded. Plasma Wnt7b levels were measured by ELISA. Diagnosis of pulmonary fibrosis (for RA-ILD and IPF patients) was done by high resolution computed tomography (HRCT) and its severity was assessed mainly by pulmonary function test using forced vital capacity (FVC) grading. RESULTS: Comparison of Wnt7b plasma levels showed a significant difference between the studied groups with the P-value < 0.018 (RA-ILD had the highest levels). Post hoc analysis revealed a significant difference in Wnt7b plasma levels between RA-ILD and IPF groups (P = 0.008). Also, RA-ILD and control groups had a significant difference (P = 0.039). However, there was a non-significant relationship between Wnt7b plasma levels and RA disease activity as well as the severity of pulmonary fibrosis. ROC curve analysis for the plasma Wnt7b levels revealed that a level  ≥285.1 pg/ml had a sensitivity of 87.5% and a specificity of 43.8% for the detection of ILD in RA patients with positive likelihood ratio of 1.56 and negative likelihood ratio of 0.29. CONCLUSION: RA-ILD patients had significantly higher plasma Wnt7b levels than the controls and IPF patients. These data suggest that the Wnt7b secretion is augmented by the concomitant presence of RA with pulmonary fibrosis. In addition, plasma Wnt7b may be used as a highly sensitive test for the detection of immunologically induced fibrotic changes in lung tissue among RA patients.

Isolated arterial mucoid intimal thickening lesion in early post-transplant kidney allograft biopsies.

INTRODUCTION: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding. METHODS: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis. RESULTS: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively). CONCLUSIONS: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important.

Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility.

Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one technique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects. It is an antimitotic medicine that regulates cell proliferation and primarily targets quickly dividing cells, and it has been related to varying levels of infertility in humans. In the current study, we assessed the biochemical, histological, and microscopic evaluations of testicular damage following cyclophosphamide administration. Further, we have explored the potential protective impact of mesenchymal stem cell (MSCs) transplantation. The biochemical results revealed that administration of cyclophosphamide increased serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while it decreased serum concentrations of free testosterone hormone (TH), testicular follicle-stimulating hormone, luteinizing hormone, and free testosterone hormone concentrations, testicular total antioxidant capacity (TAC), and testicular activity of superoxide dismutase (SOD) enzyme. The histology and sperm examinations revealed that cyclophosphamide induced destruction to the architectures of several tissues in the testes, which drastically reduced the Johnsen score as well as the spermatogenesis process. Surprisingly, transplantation of mesenchymal stem cell after cyclophosphamide administration altered the deterioration effect of cyclophosphamide injury on the testicular tissues, as demonstrated by biochemical and histological analysis. Our results indicated alleviation of serum and testicular sex hormones, as well as testicular oxidative stress markers (total antioxidant capacity and superoxide dismutase activity), and nearly restored the normal appearance of the testicular tissues, Johnsen score, and spermatogenesis process. In conclusion, our work emphasizes the protective pharmacological use of mesenchymal stem cell to mitigate the effects of cyclophosphamide on testicular tissues that impair the spermatogenesis process following chemotherapy. These findings indicate that transferring mesenchymal stem cell to chemotherapy patients could significantly improve spermatogenesis.

Topiramate affords neuroprotection in diabetic neuropathy model via downregulating spinal GFAP/inflammatory burden and improving neurofilament production.

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy.

SWI/SNF chromatin remodeling subunit Smarca4/BRG1 is essential for female fertility†.

Mammalian folliculogenesis is a complex process that involves the regulation of chromatin structure for gene expression and oocyte meiotic resumption. The SWI/SNF complex is a chromatin remodeler using either Brahma-regulated gene 1 (BRG1) or BRM (encoded by Smarca4 and Smarca2, respectively) as its catalytic subunit. SMARCA4 loss of expression is associated with a rare type of ovarian cancer; however, its function during folliculogenesis remains poorly understood. In this study, we describe the phenotype of BRG1 mutant mice to better understand its role in female fertility. Although no tumor emerged from BRG1 mutant mice, conditional depletion of Brg1 in the granulosa cells (GCs) of Brg1fl/fl;Amhr2-Cre mice caused sterility, whereas conditional depletion of Brg1 in the oocytes of Brg1fl/fl;Gdf9-Cre mice resulted in subfertility. Recovery of cumulus-oocyte complexes after natural mating or superovulation showed no significant difference in the Brg1fl/fl;Amhr2-Cre mutant mice and significantly fewer oocytes in the Brg1fl/fl;Gdf9-Cre mutant mice compared with controls, which may account for the subfertility. Interestingly, the evaluation of oocyte developmental competence by in vitro culture of retrieved two-cell embryos indicated that oocytes originating from the Brg1fl/fl;Amhr2-Cre mice did not reach the blastocyst stage and had higher rates of mitotic defects, including micronuclei. Together, these results indicate that BRG1 plays an important role in female fertility by regulating granulosa and oocyte functions during follicle growth and is needed for the acquisition of oocyte developmental competence.

Herpes Simplex Virus Esophagitis as a Presentation of Febrile Neutropenia: A Case Report.

Herpes Simplex Virus esophagitis typically manifests as mucocutaneous lesions in immunocompromised patients, most frequently in organ and bone marrow transplant recipients. However, it has not been appropriately reported as a cause of febrile neutropenia despite being a relatively common opportunistic infection in this patient population.  A 58-year-old man recently diagnosed with Ewing Sarcoma for which he was receiving chemotherapy presented with febrile neutropenia. Following a prolonged hospital course characterized by persistent fevers, an endoscopic evaluation was performed and diagnosis of Herpes Simplex Virus esophagitis was confirmed via histopathology. Prompt administration of acyclovir resulted in the complete resolution of the patient's symptoms.  Recognition of Herpes Simplex Virus esophagitis as an etiology of febrile neutropenia can ensure more prompt diagnosis and allow for appropriate management of these patients. In addition, this case report emphasizes a need for further research into additional diagnostic markers in the workup of these patients and the incorporation of antiviral therapy in febrile neutropenia algorithms.

Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complex-mediated glomerulonephritis: A case report.

BACKGROUND: Anti-glomerular basement membrane (GBM) disease is a rare rapidly progressive glomerulonephritis, frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis. It has been described in association with other glomerulonephritides [such as anti-neutrophilic antibody (ANCA)-glomerulonephritis, membranous nephropathy, and immunoglobulin (Ig)A nephropathy]. CASE SUMMARY: Herein we present an unusual case of concurrent anti-GBM disease, ANCA-associated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence. The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL, proteinuria, and hematuria. He rapidly deteriorated and became anuric. He was found to have high anti-GBM antibodies titers (151 units) and high anti-neutrophil cytoplasmic-ANCA. Despite prompt and early treatment, the patient's condition worsened, and he succumbed to his illness. CONCLUSION: Our case emphasizes the importance of a renal biopsy in anti-GBM disease, even in the presence of positive serum anti-GBM antibodies, to identify other potential causes of rapidly progressive glomerulonephritis. The challenge in treating such cases lies in the different therapy modalities.

Proteus syndrome with sciatic nerve fibrolipomatous hamartoma: an uncommon finding in a rare disease: report of two cases with literature review.

Proteus syndrome is an extremely rare condition, characterized by progressive asymmetric overgrowth of multiple body tissues. Here, we present two cases of Proteus syndrome demonstrating typical clinical and radiological features of Proteus syndrome, in addition to an uncommon fibrolipomatous hamartoma of the sciatic nerve. The first case is a 5-year-old girl who presented with seizures. The patient showed facial dysmorphic features, left head enlargement, kyphoscoliosis, asymmetric overgrowth of the right lower limb, right foot drop, and cribriform connective tissue nevi on the right palm and the right sole. Radiological examinations demonstrated left calvarial hyperostosis, dysplasia of the left cerebral hemisphere, dysregulation of the subcutaneous adipose fat of the body, kyphoscoliosis, and lipoma of the filum terminale. CT of both thighs showed asymmetric soft tissue overgrowth of the right thigh, associated with diffuse enlargement and fatty infiltration of the right sciatic nerve starting from the upper thigh, down to its bifurcation into the tibial and common peroneal nerves. The second case is an 18-year-old girl who presented with left conductive deafness. The patient showed facial dysmorphic features, right head enlargement, asymmetric overgrowth of the right upper limb, kyphoscoliosis, left foot drop, and cribriform connective tissue nevi on the nose and the left foot. Radiological examinations demonstrated right calvarial hyperostosis, left external auditory canal hyperostosis and stenosis, and kyphoscoliosis. CT and MRI of both thighs showed diffuse enlargement of the left sciatic nerve starting from the upper thigh down to the mid-thigh and showing interfascicular adipose tissue proliferation, giving the typical features of nerve lipomatosis.

Efficacy of Photoinduced Photoacoustic Streaming and Diode Laser Irrigation Techniques on Smear Layer Removal, Sealer Penetration and Push-out Bond Strength.

Introduction: The present study aimed to test the efficiency of photoinduced photoacoustic streaming using 2940 nm Er: YAG laser and 980 nm diode laser agitation on smear layer removal, sealer penetration and push-out bond strength. Methods: Sixty single canaled human permanent teeth were collected for this study. Specimens were grouped into three experimental groups (20 teeth in each group), depending on the activation protocol used for final irrigation: Group I (needle agitation), group II (980nm diode laser agitation) and group III (photon induced photoacoustic streaming (PIPS) using 2940 nm Er: YAG laser. The quantity of irrigant was standardized in all groups to 4 ml. The irrigant was activated for 40 seconds in different groups under continuous flow. Two teeth from each group were used to check the smear layer removal, and then the remaining teeth in each group were randomly divided into three equal experimental subgroups according to methods of evaluation used: subgroup A: Sealing ability evaluated by dye penetration method; subgroup B: SEM for sealer penetration; and subgroup C: Push-out bond strength assessed by the universal test machine. Results: As regards smear layer removal, results showed that the PIPS group had opened dentinal tubules, followed by the diode laser group, while the least cleaning effect was found in the Side-vented needle group. As for Sealing ability and dye penetration, a statistically significant difference was found between all of the three groups, with the Er:YAG laser (PIPS) having the best sealing ability and sealer penetration. Push-out bond strength results showed no statistically significant difference between diode and Er:YAG groups, with a significant difference between each of them and the Side-vented needle group. Conclusion: Using the diode or Er:YAG laser (PIPS) for irrigant activation led to better irrigant penetration and smear layer removal which subsequently led to obvious sealer penetration, better sealing, and strength properties of endodontic treated teeth.

Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics.

Background: Carbapenemase-producing Gram-negative bacteria, particularly Klebsiella pneumoniae (K. pneumoniae), are at the forefront of the list of causative agents of ventilator-associated pneumonia (VAP). The treatment options for such infections are limited, and various antimicrobial combinations have been suggested as alternatives in clinical practice. New antibiotics, such as ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol, have shown advantages in both in vitro and clinical studies. Purpose: To evaluate the in vitro effect of meropenem-ciprofloxacin and meropenem-colistin combinations on carbapenem-resistant (CR) K. pneumoniae VAP isolates and to determine their susceptibility to new antibiotics. Methods: Seventy-three K. pneumoniae isolates from 176 endotracheal samples from VAP cases were studied. Antibiotic susceptibility testing and phenotypic detection of extended-spectrum ß lactamase (ESBL) and carbapenemase production were done. CR K. pneumoniae isolates were tested for the five predominant carbapenemase genes (bla KPC, bla OXA-48, bla NDM, bla VIM, and bla IMP). In vitro evaluation of meropenem-ciprofloxacin and meropenem-colistin combinations was done by MIC test strips. Susceptibility to new antibiotics was tested by disk diffusion method. Results: Sixty-three (86.3%) of the isolates were ESBL producers and 52 (71.2%) were carbapenem resistant. Bla NDM was the most prevalent carbapenemase gene (50%), followed by bla OXA-48, (36.5%) then bla KPC in (11.5%). Bla VIM and bla IMP were not detected. Meropenem-ciprofloxacin combination showed indifferent effect on all isolates, while meropenem-colistin combination showed 25% synergism, 15.4% addition and 59.6% indifference. All (100%) CR K. pneumoniae isolates were resistant to ceftolozane/tazobactam and 79% were resistant to ceftazidime/avibactam, while 96% were sensitive to cefiderocol. Conclusion: A high rate of carbapenem resistance exists among VAP K. pneumoniae isolates. Meropenem-colistin combination and cefiderocol appear to be potential treatment options for infections caused by CR K. pneumoniae. Resistance to the tested new ß-lactam/ß-lactamase inhibitors was high, signifying a major threat.

Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: Behavioral psychomotor performance, neurotransmitter level, oxidative-inflammatory markers, and BDNF expression in rat brain.

Exposure to aluminum chloride (AlCl3) induces progressive multiregional neurodegeneration in animal models by promoting oxidative stress and neuroinflammation. The current study was designed to assess the potential efficacy of the natural antioxidants celastrol and thymoquinone (TQ) for alleviating AlCl3-induced psychomotor abnormalities and oxidative-inflammatory burden in male albino rats. Four treatment groups were compared: (i) a vehicle control group, (ii) a AlCL3 group receiving daily intraperitoneal (i.p.) injection of AlCl3 (10 mg/kg) for 6 weeks, (iii) a AlCl3 plus TQ (10 mg/kg, i.p.) cotreatment group, and (iv) a AlCl3 plus celastrol (1 mg/kg, i.p.) cotreatment group. Open-field, rotarod, and forced swimming tests were conducted to assess locomotor activity, motor coordination, anxiety-like behavior, and depressive-like behavior. Acetylcholine (ACh), dopamine, and serotonin levels were measured in brain homogenates. Malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity were measured as oxidative stress markers, while tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) expression levels were measured as inflammatory markers. Brain derived neurotrophic factor (BDNF) mRNA was measured as an index for the endogenous neuroprotective response. Daily AlCl3 injection reduced free ambulation, impaired motor coordination, promoted anxiety- and depression-like behaviors, reduced whole-brain ACh, dopamine, and serotonin concentrations, increased MDA accumulation, reduced TAC, elevated TNF-α and IL-6, and suppressed BDNF mRNA expression. All of these effects were significantly reversed by TQ or celastrol cotreatment. Thus, TQ and celastrol may be promising treatments for AlCl3-induced neurotoxicity as well as neurodegenerative diseases involving oxidative stress and neuroinflammation.