A novel extraoral ultrasound-guided approach for mandibular nerve block in Rahmani sheep.

BACKGROUND: Regional anesthesia is the favored choice in ruminant animals compared to general anesthesia, primarily due to its high safety margin and reduced demand for cost-intensive equipment in addition to its field applicability. Ultrasound-guided nerve block has gained significant attention in the field of veterinary medicine. This study utilized twenty-seven sheep of the native Rahmani breed to both demonstrate and evaluate the effectiveness of the ultrasound guided inferior alveolar nerve block technique. METHODS: The research comprised three phases: Phase 1 involved an anatomical examination of mandibles and sheep heads to locate the mandibular foramen and delineate the mandibular nerve course. Phase 2 included ultrasound-guided injection of methylene blue dye at specific sites along the mandibular nerve in cadaveric sheep heads. In Phase 3, clinical implementation of ultrasound-guided inferior alveolar nerve blocks was conducted in 27 live sheep, assessing efficacy, onset, and duration. RESULTS: Vertical extraoral ultrasound-guided nerve block was achieved successfully in 25 sheep (98%). A preliminary cadaveric study showed good distribution of the injectate at the mandibular nerve site. The mean onset time was 138 ± 18 s, and the mean duration time was 54 ± 4.1 min. Prominent analgesia of the ipsilateral mandible, medial surface of the cheek, and lateral border of the tongue was observed. CONCLUSIONS: Ultrasound-guided mandibular nerve block holds promise as a technique for providing effective and safe anesthesia in sheep undergoing mandibular procedures.

A novel supraorbital surgical approach for enucleation in dromedary camels (Camelus dromedaries): cadaveric study.

BACKGROUND: Enucleation and exenteration are widely utilized ophthalmic procedures in veterinary practice, involving the complete removal of the eye and comprehensive extraction of orbital contents, respectively. These procedures are indicated for pain relief, excision, and management of neoplasia metastases, and addressing severe medically untreatable conditions. AIM: This study aimed to develop an orbital enucleation surgical approach. The study evaluated the applicability of the new approach and investigated the impact of the surgical procedure. METHODS: Anatomical dissection of three cadaveric heads and surgical orbital enucleation in four cadaveric heads were performed. Anatomical data was collected, and feasibility, safety and applicability of the procedure were assessed. RESULTS: Anatomical dissection showed a distinctive large orbital fossa, providing a suitable surgical window to access orbital structures. The procedure was found to be feasible, facilitating the complete removal of the orbital content. Notably, the preservation of intact eyelids was prioritized to enhance cosmetic appearance. CONCLUSION: The presented orbital enucleation technique proved to be feasible, safe, reproducible, and required basic surgical skills to perform.

Introducing a novel intraoral mandibular nerve block technique for loco-regional analgesia in camels (Camelus dromedarius): a cadaveric study using computed tomography.

The aim of this study was to introduce a novel intraoral technique for performing mandibular nerve blocks in dromedary camels (Camelus dromedarius). In this study, 18 adult camel skulls of varying ages and breeds were examined to determine the position of the mandibular foramen. Using a Vernier caliper, three dimensions in millimeters were measured: (1) the distance between the mandibular foramen (MF) and the caudal edge of the third molar tooth at the occlusal surface level, (2) the distance between the MF and the rostral edge border of the mandible's ramus (RER) at the occlusal surface level, and (3) the distance between the MF and the ventral margin border of the mandible (VM). The technique was evaluated using five intact camel cadaver heads (n = 5), and a total of ten mandibular nerve blocks were described. An 18-gauge 80-mm Tuohy needle was inserted into the mouth commissure and advanced caudally while injecting a saline-methylene blue solution. The accuracy of the injection was confirmed through the infiltration of the contrast dye into the target area using computed tomography (CT) and post procedural dissection. Anatomical study of the mandibular nerve site was performed to aid the blind insertion of the needle. The findings contribute to the development of veterinary anesthesia techniques and provide anatomical considerations for clinicians performing oral surgeries in sedated camels. The results demonstrated the successful implementation of the intraoral technique, highlighting its efficacy and reliability in achieving local anesthesia for oral surgeries involving the lower jaw and teeth in sedated camels. Further research studies are needed to evaluate the long-term efficacy and safety of the technique and to compare it with existing approaches.

Chronic kidney disease in Kuwait: a multicenter study of two cohorts with different levels of access to public healthcare.

INTRODUCTION: Kuwait has a large expatriate community who experience both restricted access to public health services and lower income than Kuwaiti citizens. Given these conditions, we examined differences in characteristics and management of chronic kidney disease (CKD) between Kuwaitis and expatriates. METHODS: Clinical and laboratory data for adult CKD Stages 3-5 not on dialysis (CKD 3-5 ND) patients with native kidneys attending nephrology clinics in all Ministry of Health hospitals collected from January 1, 2022, to December 31, 2022. Cohort was then divided into Kuwaiti patients and expatriates patients for comparison. RESULTS: We collected data from 2,610 patients (eGFR: 30.8 ml/min/1.73m2; age: 62.6 years; males: 56.7%; Kuwaitis: 62.1%). Kuwaitis were older (63.94 vs. 60.3 years, p < 0.001), with lower mean eGFR (30.4 vs. 31.5 ml/min/1.73m2, p = 0.052) than non-Kuwaitis, however, Kuwaitis had lower mean blood pressure (137.2/76.5 vs. 139.1/78.9 mmHg, p = 0.006), lower HbA1c in diabetics (7.59 vs. 7.82%, p = 0.010), and better lipid profile despite higher body mass indexes (29.6 vs. 28.9 kg/m2, p = 0.002). Both groups had high diabetes mellitus and hypertension rates. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were used in only 22.6% and renin-angiotensin-aldosterone system inhibitors (RAASi) in only 46.2%. CONCLUSION: CKD 3-5 ND is caused by diabetes mellitus in 56.6% of cases, and the majority have hypertension. In our study, non-Kuwaitis had higher eGFR; however, restricted public healthcare access and lower income can lead to an unhealthy diet and suboptimal care, which may cause higher blood pressure, higher HbA1c, and a higher dyslipidemia rate. RAASi and SGLT2i utilization must increase to combat CKD, and antihypertensive selection must improve.

PCDH17 gene promoter methylation status in a cohort of Egyptian women with epithelial ovarian cancer.

BACKGROUND AND OBJECTIVE: Ovarian cancer is a leading cause of female mortality. Epigenetic changes occur in early stages of carcinogenesis and represent a marker for cancer diagnosis. Protocadherin 17 (PCDH17) is a tumor suppressor gene involved in cell adhesion and apoptosis. The methylation of PCDH17 gene promoter has been described in several cancers including ovarian cancer. The aim of the study was to compare the methylation status of PCDH17 gene promoter between females diagnosed with epithelial ovarian cancer and a control group composed of normal and benign ovarian lesions. METHODS: Fifty female subjects were included in our study (25 ovarian cancer patients and 25 controls). DNA was extracted from Formalin-Fixed Paraffin-Embedded (FFPE) tissues of the subjects. Methylation levels for six CpG sites in the PCDH17 gene promoter were assessed by pyrosequencing. RESULTS: The methylation levels at five out of six sites were significantly higher in females with epithelial ovarian cancer compared to the control group. Moreover, the same applies for the mean methylation level with p value 0.018. CONCLUSION: Methylation of PCDH17 gene promoter plays a role in ovarian carcinogenesis and can be used for diagnosis and early detection.

Differential vulnerability of anterior cingulate cortex cell types to diseases and drugs.

In psychiatric disorders, mismatches between disease states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell types? How does disease and drug effect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex-a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common or salient functional themes across cell types. Cell-specific signatures were integrated with existing disease and drug-specific signatures to determine cell-type-specific vulnerabilities, druggabilities, and responsiveness. Clustering of functional profiles revealed cell types jointly participating in these events. SST and VIP interneurons were found to be most vulnerable, whereas pyramidal neurons were least. Overall, the disease state is superficial layer-centric, influences cell-specific salient themes, strongly impacts disinhibitory neurons, and influences astrocyte interaction with a subset of deep-layer pyramidal neurons. In absence of disease, drugs profiles largely recapitulate disease profiles, offering a possible explanation for drug side effects. However, in presence of disease, drug activities, are deep layer-centric and involve activating a distinct subset of deep-layer pyramidal neurons to circumvent the disease state's disinhibitory circuit malfunction. These findings demonstrate a novel application of sn-RNAseq data to explain drug and disease action at a systems level.

The Efficacy of Anterior Capsulotomy and Basal Capsulectomy Adherent to Expanded Scalp Flap During Alopecia Reconstruction in Pediatric Burned Patients.

BACKGROUND: Scalp expansion is an optimal treatment for alopecia resulting from burn injuries, especially in the pediatric population through providing highly vascularized adjacent local tissues with optimal hair density, color matching, texture, and hair-bearing characteristics. The aim of this study was to evaluate the efficacy of anterior capsulotomy and basal capsulectomy adherent to expanded scalp flap during alopecia reconstruction with scalp expansion in pediatric burned patients. METHODS: The study was conducted on 127 patients with an age range of 5 to 19 years who presented with postburn alopecia accompanied by hairline loss. The patients were divided into 2 groups: group I consisted of 58 patients who were operated on using conventional technique, and group II consisted of 69 patients who were operated using modified technique including basal capsulectomy on the skull side and anterior capsulotomy on the expanded scalp flap. RESULTS: The Hairdex, a validated questionnaire of Hair-Specific Health-Related Quality of Life measures, showed that percentage of satisfaction concerning outcomes was 91.50%, psychological well-being was 95%, and self-confidence was 84.30% in group II, compared with 63%, 55.70%, and 66.20%, respectively, in group I. This significant values had a great positive effect on patient satisfaction, changing child's behavior and self-confidence. CONCLUSION: Although physiological background of tissue expansion is the same, proper flap design with anterior capsulotomy on flap undersurface and basal capsulectomy on the skull side improve results of the traditional method significantly and minimize the complication rate. These surgical modifications provide maximum benefits from expanded tissue, with restoration of the hairline and a uniform hair direction. LEVEL OF EVIDENCE: Level III, case-control study.

Protective Effect of Nigella sativa and Onion Extract against 5-Fluorouracil-Induced Hepatic Toxicity.

Aim: The present study intended to compare the antioxidant, anti-lipid peroxidation, and anti-inflammatory potentials of Nigella Sativa (NS) and onion extract on 5-FU-induced liver damage in rats. Material and methods: 48 rats were divided into control, control group of the onion extract, control group of the NS extract, 5-FU-treated, concomitant NS-treated, and concomitant onion extract-treated. Liver sections were processed for histological analysis (light and electron microscopic examination). Liver enzymes (ALT, AST, and ALP), inflammatory markers (TNF-α and IL-1), antioxidant markers (SOD, GSH, and GSH/GSSG ratio), 4-HNE, NF-κB, and Nrf2 were evaluated. Results: The 5-FU-treated group exhibited inflammation, congested hepatic sinusoid, and steatosis. Improvement with few pathological residues was seen in the concomitant extract-treated groups. The 5-FU-treated group showed higher liver enzymes. The enzymes decreased in the concomitantly treated groups. 5-FU induced liver damage through oxidative stress, inflammation, and lipid peroxidation. Concomitantly using NS and onion extracts resulted in a reduction in oxidative stress, lipid peroxidation, and inflammation. Conclusion: NS and onion extracts attenuated 5-FU-induced liver damage via antioxidative, anti-lipid peroxidative, and anti-inflammatory mechanisms. NS's role was exceptional when compared with onion extract.

Managing iatrogenic aortic dissection during primary percutaneous coronary intervention of the left main stem.

Iatrogenic aortic dissection post primary percutaneous coronary intervention (PCI) is rare but yet a serious complication. In this report, we present a case of a 40-year-old lady who had an aortic dissection post PCI which was initially missed by the conventional contrast images and required a gated computerized tomography aortogram to confirm the diagnosis. The patient was managed with strict blood pressure control resulting in complete healing of the dissection after 72 hours of the management. The case illustrates the importance of selecting the correct imaging to make an accurate diagnosis when aortic dissection is suspected and outlines the importance of blood pressure control in treating iatrogenic aortic dissections.

Mitral valve paravalvular leaks: Comprehensive review of literature.

BACKGROUND: Mitral paravalvular leaks (mPVL) are a recognized complication for patients with mitral valve prostheses. Although clinically insignificant for many patients, it may pose life-threatening haemolysis and regurgitation-induced heart failure, and so clinicians should have a high index of suspicion in the presence of new symptoms. AIMS: This review discusses the pathogenesis, clinical features, diagnosis, imaging and treatment of mPVLs. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, Cochrane database, Google Scholar and Ovid. Search terms used included "mitral valve paravalvular leak," "transthoracic echocardiography," "2D transoesophageal echocardiography," "3D transoesophageal echocardiography," "cardiac computed tomography," (CT) "cardiac magnetic resonance imaging," "intracardiac echocardiography," "cinefluoroscopy," "fluoroscopy," and "percutaneous closure." RESULTS: All patients with mPVLs should undergo regular full evaluation, including patient history, physical examination, laboratory work-up, imaging, and referral, if necessary. Echocardiography is fundamental to the diagnosis, and is augmented with cardiac magnetic resonance imaging, cardiac computerized tomography and fluoroscopy for further characterization and procedural planning amongst the structural heart team. CONCLUSION: The prevalence of mPVL is expected to increase proportionally to the growing number of surgical and transcatheter valve replacements conducted in the ageing population. Multimodal imaging is instrumental in guiding diagnostic and therapeutic strategies when managing mPVLs. Advances in imaging and capabilities of transcather devices will prompt growing uptake of percutaneous treatment over conventional, higher-risk surgery for mPVL management.

The management of paravalvular leaks post aortic valve replacement.

BACKGROUND: Paravalvular leak (PVL) is uncommon but can lead to severe complications after surgical or transcatheter aortic valve implantation. Conditions associated with PVLs such as heart failure, hemolysis, and infective endocarditis can lead to catastrophic results if not treated promptly; the therapeutic goals differ according to the presentation. It is vital that PVLs are diagnosed early using various imaging modalities. Different approaches have been studied in managing PVLs; there is an increased interest in the transcatheter aortic valve closure procedure as it is minimally invasive and decreases the occurrence of further reinterventions. AIM: To discuss the classification of PVLs, diagnostic approaches, and available management options. METHOD: A literature review was performed using 28 studies. RESULTS: This review evaluated the relationship between the time of diagnosis, management of PVL and the resulting outcomes. DISCUSSION: Patients with PVL should be assessed through a multidisciplinary team approach and a patient-selective plan should be in place. CONCLUSION: Open surgical intervention is reserved for complex cases where minimally invasive techniques cannot be utilized.

Minimally Invasive Reduction and Fixation Techniques of Pilon Fractures Based on the Preoperative CT Findings.

Tibial plafond fractures are often associated with significant articular cartilage and soft tissue damage. The presence of co-morbidities has been associated with an increased risk of surgical site complications. With improved in surgical techniques and implants, complication rates have declined; however, the overall prognosis often remains poor. The aims of this study were to evaluate the results of innovative minimally invasive reduction and fixation techniques in tibial plafond fractures based on a CT classification and to compare the difference between short and long-term outcomes. Based on preoperative CT findings, fractures were classified into varus, valgus, anterior, posterior, and neutral types. The minimally invasive reduction and fixation techniques depend on type of fracture, size and location of the intraarticular fragments, and degree of comminution of the extra-articular component. Ninety-one pilon fractures (90 patients) underwent minimally invasive reduction and fixation, of which 7 fractures (7.69%), required open reduction because of intraoperative failure to achieve anatomic reduction. Of the 84 fractures that underwent successful minimally invasive reduction and fixation reported, 35 fractures (41.7%) with excellent outcomes, 40 fractures (47.6%) with good outcomes, 6 fractures (7,1%) with fair outcomes, and 3 fractures (3.6%) had poor outcomes for the long-term American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score (follow-up ≥ 60 months). These results prove that minimally invasive treatment is an effective and durable treatment option for intra-articular pilon fractures. We encourage future clinical studies to further refine minimally invasive techniques for pilon fractures to improve outcomes.

Length of Barrett's esophagus in the presence of low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.

INTRODUCTION: The identification and follow-up of ultra-short Barrett's esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE. METHODS: Endoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE. RESULTS: 99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long. CONCLUSION: Almost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.

Refractory neovascular age-related macular degeneration: time-dependent changes of central retinal thickness with anti-VEGF treatment.

PURPOSE: To assess the influence of time interval since last injection and time from baseline on central retinal thickness (CRT) in neovascular age-related macular degeneration (nAMD) with fluid refractory to monthly anti-VEGF treatment. METHODS: This retrospective study included nAMD eyes with incomplete response to anti-VEGF defined by the presence of intra- or subretinal fluid on optical coherence tomography despite maximal (monthly) anti-VEGF dosing. The outcome measure was CRT, and two time variables (time from last injection ant time from baseline) were the independent factors included in the individual correlation analyses. In addition, an association analysis was performed. RESULTS: Sixty eyes of 56 patients (67.9% females, mean age: 78.7 ± 6.8 years) were included with a mean included time period of 35.6 months. A significant positive correlation between CRT and the time from last injection occurred in 24 (40%) and 25 (42%) eyes by univariate and multivariate analysis, respectively. Time from baseline was significantly correlated with CRT in 29 (48.3%) and 30 (50%) eyes by univariate and multivariate analysis, respectively. This correlation was positive in 12 (20%) and negative in 18 eyes (30%). No association with such correlation was found. CONCLUSION: So-called refractory nAMD frequently shows a correlation of CRT with the interval in days from the preceding anti-VEGF injection, revealing that there is a subgroup of short-term responsiveness of the residual fluid. Moreover, slower CRT changes may occur over the years, either decrease or increase. In case of a slow CRT increase, this might require a diagnostic workup and therapeutic change.

Cellular and molecular alterations of buffalo oocytes cultured under two different levels of oxygen tension during in vitro maturation.

This study was conducted to monitor the cellular and molecular changes of buffalo cumulus-oocytes complexes (COCs) cultured under high or low oxygen levels. Morphologically good quality COCs (n = 1627) were screened using brilliant cresyl blue (BCB) staining and placed into three groups (BCB+, BCB- and control). All groups of COCs were cultured under low (5%) or high (20%) oxygen tensions. Intracellular and molecular changes including oocyte ultrastructure, lipid contents, mitochondrial activity and transcript abundance of genes regulating different pathways were analyzed in the matured oocyte groups. The results revealed that oxygen tension did not affect cumulus expansion rates, however the BCB+ group had a higher (P ≤ 0.05) expansion rate compared with the BCB- group. BCB- oocytes recorded the lowest meiotic progression rate (P ≤ 0.05) under high oxygen levels that was linked with an increased level of reactive oxygen species (ROS) compared with the BCB+ oocytes. Ultrastructure examination indicated that BCB+ oocytes had a higher rate of cortical granules migration compared with BCB- under low oxygen tension. In parallel, our results indicated the upregulation of NFE2L2 in groups of oocytes cultured under high oxygen tension that was coupled with reduced mitochondrial activity. In contrast, the expression levels of MAPK14 and CPT2 genes were increased (P ≤ 0.05) in groups of oocytes cultured under low compared with high oxygen tension that was subsequently associated with increased mitochondrial activity. In conclusion, data from the present investigation indicated that low oxygen tension is a favourable condition for maintaining the mitochondrial activity required for nuclear maturation of buffalo oocytes. However, low-quality oocytes (BCB-) responded negatively to high oxygen tension by reducing the expression of gene-regulating metabolic activity (CPT2). This action was an attempt by BCB- oocytes to reduce the increased levels of endogenously produced ROS that was coupled with decreased expression of the gene controlling meiotic progression (MAPK14) in addition to nuclear maturation rate.

A comparative prospective study between stemmed versus an unstemmed tibial component in total knee arthroplasty in obese patients.

BACKGROUND: There is no consensus in the literature regarding the patients with obesity who do well with TKA, or this group is at risk of a variety of complications. Implant choices between the two types of implants which either long or standard stem can improve the likelihood that a patient with obesity will achieve high scores for function and quality of life after TKA. METHODS: This prospective clinical study included 200 patients who were categorized into two groups: group (1) traditional (standard) unstemmed cemented tibial tray (n = 100 patients) and group (2) stemmed cemented tibial tray with the cementless press-fit stem (n = 100 patients). RESULTS: The average follow-up was (7.6 ± 1 years) (range from 6.5 up to 10 years). The average age of the stemmed group was 55.69 ± 8.45 and for the unstemmed group was 57.3 ± 7.8. The average BMI for the stemmed patients was 38.84 ± 3.89, while for the standard (unstemmed) group was 40.0 ± 3.95. Functional results showed significant improvement in both groups but more in the stemmed group (LS) as the difference and change between pre and post were more significant at long stem (P > 0.001). CONCLUSION: Based on our results, there were significant improvements in both groups either stemmed or unstemmed TKA but more in the stemmed group which had higher functional outcomes compared to the unstemmed group. LEVEL OF EVIDENCE: IV.

Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage.

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.

Predictors of therapeutic failure among patients with acute brucellosis treated by dual therapy with doxycycline-rifampin.

OBJECTIVE: To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure. METHODS: The study included 213 consecutive, naïve patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks. RESULTS: Mean age of the study population was 39.8 ± 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9-24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5-17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2-19.5, P: 0.037) as the predictors of therapeutic failure. CONCLUSIONS: The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy.

Normal Visual Recovery after Optic Neuritis Despite Significant Loss of Retinal Ganglion Cells in Patients with Multiple Sclerosis.

BACKGROUND: Optic neuritis (ON) is a frequent manifestation of demyelinating attack in multiple sclerosis (MS). Initial visual loss can vary from minimal to complete. Visual improvement occurs in about 95% of patients, some of them recovering to normal [visual acuity (VA), color vision, visual field (VF)]. We analyzed retinal ganglion cell layer (RGCL) thickness in MS patients who recovered their normal vision after ON to determine whether a relative preservation of RGCL existed in these patients. MATERIALS AND METHODS: We conducted a retrospective study of all patients with MS and ON examined by one of us (F. X. B.) between 2013 and 2018. Inclusion criteria were strictly unilateral ON, full recovery of vision, computerized visual field, and OCT examinations. Full recovery of vision was defined as VA ≥ 10/10, Ishihara ≥ 11/13, and VF mean defect (MD) ≤ 2.6 dB. Evaluation of RGCL was obtained with spectral domain optical coherence tomography (SD-OCT). The normal fellow eye of all patients served as the control group. Relative thinning of RGCL, expressed as percentage, was calculated by comparing results from the affected eye to the fellow eye of the same patient. RESULTS: Twenty-one patients (21 affected eyes - Group 1, 21 normal fellow eyes - Group 2) satisfying the inclusion criteria were retrieved from our database. All patients exhibited the relapsing-remitting form of MS. There were 16 women and 5 men. Mean age was 39.3 years old. There were no statistically significant differences between Group 1 and Group 2 for either VA (p = 0.3934) or Ishihara (p = 0.140), but a significant difference was found for VF MD (p = 0.0405). A markedly significant difference for RGCL thickness (p = 0.0001) was found, without any correlation with the degree of visual recovery. A subgroup of patients (n = 14) was examined at the time of initial visual loss. We correlated their results of visual function to the final RGCL thickness, and a correlation was found between either the initial VA loss or the initial VF loss and the final loss of RGCL (R2 = 0.4075 and R2 = 0.00739, respectively). CONCLUSIONS: In our study, all patients with ON lost a significant amount of RGCL despite a full recovery of vision, as defined by our criteria. The percentage of RGCL loss varied from 5 - 27% and could not be correlated with any final visual indices. However, a correlation was found with the degree of initial visual loss. Despite sometimes marked RGCL loss after ON, patients with MS can recover normal visual function, according to standard clinical tests.

Cannabinoid-glutamate interactions and neural oscillations: implications for psychosis.

Preclinical and clinical data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ), the prototypical psychotic disorder. This has led to distinct "cannabis" and "ketamine" models of SZ, respectively. However, these two models need not be mutually exclusive. Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptor type 1 (CB1Rs) and glutamate N-methyl-D-aspartate receptors (NMDARs) have direct and indirect interactions. CB1R agonists and NMDAR antagonists act upon gamma-aminobutyric acid (GABA) interneurons to reduce GABAergic neurotransmission. This would be predicted to result in the unsynchronized activity of pyramidal neurons, disrupting neural network oscillations involved in information processing, thus leading to psychotomimetic effects. Hence, the overarching aim of the current review is to synthesize the known literature on cannabinoids and glutamate in the context of neural oscillations in SZ. First, discussion of SZ and the basic mechanisms of neural oscillations are discussed, including a summary of the role of theta (4-7 Hz) and gamma (30-80 Hz) oscillations in neurocognition. Next, a brief review of the role of the cannabinoid and glutamatergic systems in SZ is outlined, followed by discussion of the known synaptic interactions between these two systems. Finally, the potential role of CB1Rs and NMDARs, both independently and in combination, on neural oscillations in relation to psychotic symptoms is considered. It is hoped that this review will yield a series of testable hypotheses that may be used to further elucidate the pathophysiology of SZ.