Mild Degeneration Research Articles

Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

Hereditary sensory autonomic neuropathy type VI in the age of genetic testing

AbstractBackgroundHereditary sensory and autonomic neuropathy type VI (HSAN VI) is a rare recessive genetic disorder caused by mutations in the human dystonin (DST) gene. We report a novel homozygous alternate transcript mutation in the DST gene causing a severe neonatal form of HSAN VI.Patient DescriptionThis baby boy was born with severe hypotonia, respiratory distress, dysmorphic features, and bilateral club feet. Imaging, karyotyping, Prader–Willi assay, spinal muscular atrophy genetic panel and myotonic dystrophy genetic panel were all negative. A comprehensive neuropathy panel detected a homozygous pathogenic variant in the DST gene—alternate transcript NM_015546.4:c.1357G>A (p.Trp4525*). Nerve conduction studies revealed mixed axonal and demyelinating sensorimotor neuropathy, suggesting the possibility of motor involvement in severe forms of this rare condition. The infant ultimately developed sepsis and died from cardiorespiratory arrest. Neuropathological findings of focal and mild spinal nerve axonal degeneration were nonspecific.ConclusionCollective analysis of these patients would help to further characterize the spectrum of disease pathology and could provide insight into the neurophysiology and neuropathology of this rare condition.

The clinical application value of 3.0T magnetic resonance T2 mapping imaging in evaluating the degree of acetabular cartilage degeneration in joint replacement surgery running title: MRI and acetabular cartilage degeneration

BackgroundTo explore and compare the values of 3.0T magnetic resonance imaging (MRI) T2 mapping in evaluating the degree of acetabular cartilage degeneration in hip replacement surgery.MethodsA total of 26 elderly patients with femoral neck fractures who were scanned in 3.0T MRI T2 mapping quantification technique were included. Basing on MRI images, the degree of acetabular cartilage degeneration was classified into Grade 0, 1, 2, 3 and 4, according to the International Cartilage Repair Society (ICRS) scores. In addition, 8 healthy volunteers were included for control group.ResultsBy comparison with health population, T2 relaxation values in the anterior, superior, and posterior regions of acetabular cartilage in patients with femoral neck fracture were obviously increased (P < 0.001). Among the patients with femoral neck fractures, there were 16 hip joint with Grade 1–2 (mild degeneration subgroup) and 10 hip joints with Grade 3–4 (severe degeneration subgroup), accounting for 61.54% and 38.46%, respectively. Additionally, T2 relaxation values in the anterior and superior bands of articular cartilage were positively related to the MRI-based grading (P < 0.05); while there was no significant difference of T2 relaxation values in the posterior areas of articular cartilage between severe degeneration subgroup and mild degeneration subgroup (P > 0.05). Importantly, acetabular cartilage degeneration can be detected through signal changes of T2 mapping pseudo-color images.Conclusion3.0T MRI T2 mapping technology can be used to determine the degree of acetabular cartilage degeneration, which can effectively monitor the disease course.

Investigating the characteristics of mild intervertebral disc degeneration at various age stages using single-cell genomics.

Introduction: Intervertebral disc degeneration often occurs in the elderly population, but in recent years, there has been an increasing incidence of disc degeneration in younger individuals, primarily with mild degeneration. Methods: In order to explore the underlying mechanisms of disc degeneration in both young and aging individuals, we collected four types of nucleus pulposus (NP) single-cell sequencing samples for analysis based on Pfirrmann grading: normal-young (NY) (Grade I), normal-old (NO) (Grade I), mild degenerative-young (MY) (Grade II-III), and mild degenerative-old (MO) (Grade II-III). Results: We found that most NP cells in NO and MY samples exhibited oxidative stress, which may be important pathogenic factors in NO and MY groups. On the other hand, NP cells in MO group exhibited endoplasmic reticulum stress. In terms of inflammation, myeloid cells were mainly present in the degenerative group, with the MY group showing a stronger immune response compared to the MO group. Interestingly, dendritic cells in the myeloid lineage played a critical role in the process of mild degeneration. Discussion: Our study investigated the molecular mechanisms of intervertebral disc degeneration from an age perspective, providing insights for improving treatment strategies for patients with disc degeneration at different age groups.

Ripe Musa sapientum Peels Exhibit Neuroprotection Against Lead Acetate-Induced Brain Damage in Wistar Rats

Objective: Human health has continued to be at risk from lead exposure. This study explored the antioxidative potential of ethanol extract of ripe Musa sapientum peels to protect against lead acetate-induced neuronal insult in female wistar rats. Methods: Thirty adult female rats (120-160 g) were randomly divided into six groups (n = 5): Group 1 (control group) received 10 mL/kg of distilled water; Group 2 received 100 mg/kg lead acetate. Group 3 received 2.5 mg/kg of donepezil. Groups 4 to 6 received 100, 200, and 400 mg/kg ethanol extract of ripe M sapientum, respectively, via oral gavage. Groups 2 to 5 were co-treated with 100 mg/kg lead acetate for 21 days. Neurobehavioral parameter, biochemical and histological analyses of the hippocampus were determined. Recognition memory was evaluated using Novel Object Recognition Test. Results: There was a significant ( p &lt; 0.05) increase in total exploration, discrimination index, and percentage alternation in the ethanol extract M sapientum-treated groups compared with the lead acetate-induced group. M sapientum ethanol extract and dopamine significantly ( p &lt; 0.05) reduced acetylcholinesterase enzyme (AChE) and malondialdehyde (MDA) activities in a dose-dependent manner and significantly ( p &lt; 0.05) increased superoxide dismutase activity (SOD) dose dependently, respectively. In the histopathological analysis of the hippocampal area, there were mild vacuolation (V), mild degeneration as well as mild granular cell atrophy in the treated groups, suggesting that M sapientum may have neuroprotective properties. Conclusion: Ethanol extract of ripe M sapientum peels enhanced cognitive functions and may be beneficial in preventing neurodegenerative disorders via antioxidant mechanism.

Evaluation of the acute and sub-acute toxicity of the standardized extract of Avicennia officinalis L. in mice

Avicennia officinalis L. (AOL) has shown promise for its anti-inflammatory, anti-cancer, and antioxidant properties. However, there is no research on the toxicity of this plant in Vietnam. The acute and sub-acute toxicology study proved that AOL leaf extracts are practically non-toxic in normal mice. Acute toxicity assessment was conducted with single oral doses of AOL extract (2500, 3100, 4100, and 5000 mg/kg). In sub-acute toxicity, mice were administered daily oral doses of AOL extract (200 and 400 mg/kg) for 28 days. Blood was collected from the heart, liver, and kidneys for further analysis. The comprehensive results revealed an oral median lethal dose (LD50) exceeding 5000 mg/kg, indicating low acute toxicity. A sub-acute study (200 and 400 mg/kg/day) showed no deaths or weight gain. At both doses, the standardized AOL extracts decreased serum aspartate transaminase activity. Administration of the 200 mg/kg group significantly increased blood urea levels; however, histological examination of mouse kidneys in this group revealed no signal of damage. Histological examination of mouse livers revealed mild degeneration, possibly due to the use of adult mice and potentially unrelated to the extract. This study emphasizes AOL's potential for further pharmacological testing based on its low acute toxicity and promising results.

Investigation of the Relationship Between Cervical Vertebral Column Degeneration and Posterior Circulation Perfusion Area Ischemia

Aim: The primary objective of this study was to establish whether degeneration of the cervical vertebrae and paravertebral structures serves as a predisposing factor for ischemic processes by disrupting hemodynamics in the posterior system through mechanical effects on the vertebral arteries. Material and Method: We conducted a retrospective analysis of 180 patients who underwent various imaging tests between January 2017 and October 2023. These tests included cervical magnetic resonance imaging (MRI), cervical computed tomography (CT), carotid-vertebral neck CT angiography (CTA), cranial CT, and cranial MRI. Of the 180 patients, 90 had mild degeneration or no significant degeneration, with a mean age of 58 years, and 90 had significant cervical spondylosis (CS) with a mean age of 64 years. The radiological findings were statistically analyzed, and a p-value of less than 0.05 was considered statistically significant. Results: There was no significant difference between age and parenchymal density in the control group (p=0.09). There was no statistically significant difference between the age and parenchymal density in the CS group (p=0.07). As CS became more severe, there was a statistically significant increase in the incidence of atrophic enlargement of the cerebellar folia and loss of density in the posterior fossa (p=0.03) and posterior circulation infarcts (POCI) (p=0.04). Conclusion: When severe, CS can adversely affect vascular hemodynamics in the posterior system, predisposing perfused neural parenchyma to ischemia.

Exploring the Early Molecular Pathogenesis of Osteoarthritis Using Differential Network Analysis of Human Synovial Fluid

The molecular mechanisms that drive the onset and development of osteoarthritis (OA) remain largely unknown. In this exploratory study, we used a proteomic platform (SOMAscan assay) to measure the relative abundance of more than 6000 proteins in synovial fluid (SF) from knees of human donors with healthy or mildly degenerated tissues, and knees with late-stage OA from patients undergoing knee replacement surgery. Using a linear mixed effects model, we estimated the differential abundance of 6251 proteins between the three groups. We found 583 proteins upregulated in the late-stage OA, including MMP1, collagenase 3 and interleukin-6. Further, we selected 760 proteins (800 aptamers) based on absolute fold changes between the healthy and mild degeneration groups. To those, we applied Gaussian Graphical Models (GGMs) to analyze the conditional dependence of proteins and to identify key proteins and subnetworks involved in early OA pathogenesis. After regularization and stability selection, we identified 102 proteins involved in GGM networks. Notably, network complexity was lost in the protein graph for mild degeneration when compared to controls, suggesting a disruption in the regular protein interplay. Furthermore, among our main findings were several downregulated (in mild degeneration versus healthy) proteins with unique interactions in the healthy group, one of which, SLCO5A1, has not previously been associated with OA. Our results suggest that this protein is important for healthy joint function. Further, our data suggests that SF proteomics, combined with GGMs, can reveal novel insights into the molecular pathogenesis and identification of biomarker candidates for early-stage OA.

Spinopelvic interactions in total hip arthroplasty: 295 patients followed for a minimum follow-up of 10 years.

Concurrent spinal pathology is frequent in patients undergoing total hip arthroplasty (THA). In this study we examined whether spinopelvic interactions affect THA outcomes at a minimum follow-up of 10 years. 295 patients with a mean age of 63.3 (range 56‒80) years receiving a THA between 2006 and 2009 were assessed. Of these, 195 had mild lumbar disc degeneration and 100 had advanced lumbar spondylosis. We analysed the changes in the Harris Hip Score (HHS) and the survival rate for postoperative low back pain (LBP) and dislocation. Changes in acetabular component position, sacro-femoral-pubic (SFP) and pelvic obliquity (PO) angles were assessed with radiological images. The mean HHS was lower in female patients (p = 0.009), patients >65 years of age (p < 0.001) and those with advanced lumbar spondylosis (p = 0.002). 52 (71.2%) of the patients reporting preoperative LBP experienced improvement after THA while 47 (21.1%) of those without preoperative LBP postoperatively reported new onset LBP. Female patients (p = 0.025; hazard ratio [HR]: 1.831; 95% CI, 1.081-3.101) and those with preoperative LBP (p = 0.007; HR 2.068; 95% CI, 1.221-3.504) were at a higher risk of developing postoperative LBP at 10 years. 4 out of 9 THA dislocations were late and had shown decreasing SFP angle values over time. Acetabular component inclination and anteversion angles increased over time, whereas the SFP angle was associated with sex and age and the PO angle with age and the severity of any preoperative lumbar degeneration. Concurrent spinal pathology influences THA outcomes at a minimum follow-up of 10 years. Sex, age, and associated lumbar degeneration can affect clinical and radiological changes over time. A decrease in SFP angle values over time was found in patients sustaining late dislocation.

Synergistic Effect of Naringin and Glimepiride in Streptozotocin-induced Diabetic Rats.

Evaluation of the synergistic effect of Naringin and Glimepiride in streptozotocin (STZ)-induced diabetic rats. Wistar rats were chosen and divided into five groups (n=6). STZ was used for the induction of diabetes. The combination of naringin and glimepiride was administered to diabetic rats. The changes in fasting blood sugar, body weight, Hb, HbA1c, and creatinine were evaluated, and urine was collected and the volume was observed. The lipid profiles like TC, HDL, LDL, and TG were measured. The biochemical parameters SGOT, SGPT, and ALP were analysed. Besides, endogenous antioxidant parameters like SOD, GSH, and catalase were also assessed. Lastly, the histopathological study of the beta cells in islets of the pancreas, glomerulus, and tubules of kidney and liver cells was conducted in all groups. The result shows significant reduction (p<0.001) of blood sugar in the naringin and glimepiride-treated group when compared with the control group (diabetes). Additionally, the combination of Naringin (100 mg/kg) and Glimepiride (0.1 mg/kg) significantly restores the creatinine levels and urine volumes, SGOT, SGPT, and ALP when compared to a single dose of administration. Further, the abnormal lipid profile levels (TC, LDL, TG, and HDL), and endogenous antioxidant enzymes (SOD, GSH, catalase) in diabetic control rats were restored to normal levels in a significant manner. The histopathological result reveals significant alterations, including hypertrophy of islets and mild degeneration, renal necrosis, and inflammation of hepatocytes. A synergistic effect of Naringin and glimepiride was observed during the estimation of various biochemical parameters like body weight, fasting blood sugar, creatinine, urine level, TG, total cholesterol, SGOT, SGPT, ALP, Insulin, HbA1c, antioxidant parameters like SOD, GSH, and catalase in STZ-induced diabetic rats. Further, the combination of therapy improves the protective effect of the pancreas, kidney, and liver, suggesting a potential antidiabetic effect.

Nigrostriatal degeneration determines dynamics of glial inflammatory and phagocytic activity

Glial cells are key players in the initiation of innate immunity in neurodegeneration. Upon damage, they switch their basal activation state and acquire new functions in a context and time-dependent manner. Since modulation of neuroinflammation is becoming an interesting approach for the treatment of neurodegenerative diseases, it is crucial to understand the specific contribution of these cells to the inflammatory reaction and to select experimental models that recapitulate what occurs in the human disease. Previously, we have characterized a region-specific activation pattern of CD11b+ cells and astrocytes in the α-synuclein overexpression mouse model of Parkinson´s disease (PD). In this study we hypothesized that the time and the intensity of dopaminergic neuronal death would promote different glial activation states. Dopaminergic degeneration was induced with two administration regimens of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), subacute (sMPTP) and chronic (cMPTP). Our results show that in the sMPTP mouse model, the pro-inflammatory phenotype of striatal CD11b+ cells was counteracted by an anti-inflammatory astrocytic profile. In the midbrain the roles were inverted, CD11b+ cells exhibited an anti-inflammatory profile and astrocytes were pro-inflammatory. The overall response generated resulted in decreased CD4 T cell infiltration in both regions. Chronic MPTP exposure resulted in a mild and prolonged neuronal degeneration that generated a pro-inflammatory response and increased CD4 T cell infiltration in both regions. At the onset of the neurodegenerative process, microglia and astrocytes cooperated in the removal of dopaminergic terminals. With time, only microglia maintained the phagocytic activity. In the ventral midbrain, astrocytes were the main phagocytic mediators at early stages of degeneration while microglia were the major phagocytic cells in the chronic state. In this scenario, we questioned which activation pattern recapitulates better the features of glial activation in PD. Glial activation in the cMPTP mouse model reflects many pathways of their corresponding counterparts in the human brain with advanced PD. Altogether, our results point toward a context-dependent cooperativity of microglia/myeloid cells and astrocytes in response to neuronal damage and the relevance of selecting the right experimental models for the study of neuroinflammation.Graphical abstract

Histopathological effect of Buccholzia coricea on some liver and kidneys in alloxan-induced diabetic Wistar rats

Liver and kidneys are vital organs that play several important roles such as detoxification, storage of blood, blood filtration and purification, urine excretion and secretion of hormones among others. This study was conducted to determine the histopathological effects of Buccholzia coricea on the liver and kidneys of female wistar rats, Twenty-five female wistar rats were divided into five groups of five rats per group. The five rats in group one served as the normal control group and were fed with food and water without inducement and treatment. Test group two, the positive control were induced with alloxan (150 mg/kg) without any treatment throughout the study. Test group three, the known drug group were induced with diabetes (150 mg/kg) and administered metformin daily. Test group four were induced with diabetes and were treated with low dose of 250 mg/kg of Buccholzia coriacea seed extract daily throughout the study. Test group five were induced with diabetes and were treated with high dose of 1000 mg/kg of Buccholzia coriacea seed extract daily throughout the study for 14 days and the animal models were checked daily with glucometer to ascertain their blood sugar level before the animals were sacrificed and organs harvested and preserved for histological analysis. At the end of the 14 days, hematoxylin and eosin staining methods of histological methods were used. The results of the histology of the five groups showed that group one had normal liver and kidney tissues. Group two showed cytoplasmic vacoulation and cellular infiltration of liver but an inflammation of the kidney tissue. Group three had mild sinusoidal dilation in the liver and distention of the renal tubules with reduced inflammation of the kidney tissue. Group four had cytoplasmic vacoulation of liver and reduced inflammatory activities of the kidney tissue. Group five had mild cellular degeneration of liver, hemorrhage and inflammation of the kidney tissue. Thus, Buccholzia coriacea can improve the functioning of the liver and kidneys of a diabetic rats when it is consumed below 1000mg and its equivalent daily by mitigation of the histopathological alterations by alloxan-induced diabetes. Buccholzia coriacea is a natural panacea in the management of diabetes-related organ damage.

Effects of calcium carbide ripened banana on organ weight, histological architecture and semen profile on male albino Wistar rats

Fruits play an important role in human diets, providing essential nutrients and helping to prevent disease. However, concerns arise regarding their impact on male reproductive health due to potential exposure to pesticides, heavy metals, and artificial ripening agents. This study investigates the acute and chronic effects of calcium carbide-ripened bananas on testicular weight and histological architecture, and semen profile in adult male Wistar rats. A 14-week experiment involved acclimatization, followed by acute (4 weeks) and chronic (12 weeks) phases, with rats divided into control and various banana-treated groups. Notably, in the chronic phase, significant decreases in relative testicular weight were observed in rats administered 200mg/kg of calcium carbide-ripened bananas compared with the control and with those treated with normal ripe banana respectively. Significant reductions in sperm motility and total sperm count were noted in group D in the acute phase when compared with the group treated with normal ripe banana. Increased levels of active spermatogonia and spermatogenesis were observed in the rats administered with normal ripened banana, with mild degeneration of germinal epithelium in the chronic phase, particularly in the calcium carbide-ripened banana-treated groups. These findings may suggest potential adverse effects of calcium carbide-ripened bananas on male reproductive health, warranting further investigation into their safety and regulation.

Effect of Prebiotic, Probiotic Bacteria and Symbiotic Diets Containing Bacillus Coagulans and Gum Arabic on Lipid Profile in Hypercholesterolemic Rats

Purpose: Hypercholesterolemia poses a significant challenge for numerous communities and healthcare professionals because of the association between cardiovascular conditions and dyslipidemia. The objective of this research was to assess the impact of prebiotics, probiotics, as well as a diet incorporating Bacillus coagulants and gum Arabic on blood lipid levels in hypercholesterolemic rats.&#x0D; Methodology: In order to create an antiseptic solution, acquire the organic substance known as gum Arabic. Thirty-five male Albino rats (170 ± 5 g) were feeding a prepared diet includes supplemented cholesterol to raise the levels of cholesterol. Mice were divided to 5 groups (n = 7). Group 1: simple diet (negative control), the other 4 groups were assigned for a hypercholesterolemia diet comprising 25% lard and 2% cholesterol for 6 weeks in order to increase fat cholesterol in rats. Group 2: (positive control), Group 3: fed with a supplement including 5% gum Arabic (prebiotic), Group 4: fed with a dietary supplement comprising coagulase spores, Group 5: assigned for a simple meal. It was supplemented with 5% daily gum Arabic and Bacillus coagulants spores (symbiotic).&#x0D; Results: Triglyceride levels and total cholesterol (mg/dL) were improved (P&lt;0.05). In (advantageous manipulate) fed a simple diet (B.D.), compared with (poor manipulate).&#x0D; Unique Contribution to theory, Practice and Policy: The Anti-Inflammatory Theory and the concept of prebiotics usage to decrease cholesterol and minimize its absorption. This shows that the concept used has been validated. The satisfactory results which confirmed the extreme spread variations with the poor manipulate organization had been done within side the hypercholesterolemia organizations include with Gum Arabic (GA5%), where the best indicated a fee recorded (28.54 ± 3. seventy one mg/dL), which transferred into the poor manipulate (36.33 ± 5.00 mg/dL). As for the organizations that took B. coagulants and GA 5% + B. coagulants, a lower in LDL-c, (VLDL-c), levels of AST and AST, and the satisfactory outcome documented and directed within side of the organization GA 5% + B.Coagulants. Histological checkups furthermore confirmed that the liver sections inside the 5th organization established a regular structure, also the liver cells mild degeneration. CONCLUSION: The satisfactory final outcome indicated within side the organization of GA 5%+ B. coagulants remedy organization compared with the opposite organizations.

Investigation of Potential Protective effects of Betanin on experimental Monosodium Glutamate–induced toxicity in Elderly rats

This study was conducted to investigate the protective effects of Betanin active ingredient in red beetroot plant (Beta vulgaris) in elderly rats exposed to chronic toxicity of monosodium glutamate (MSG). A total of 48 elderly rats were randomly divided into 4 different groups. At the end of the 28–day study, the rats were sacrificed under deep anesthesia. Total antioxidant capacity (TAC), total oxidant capacity (TOC), paraoxonase (PON), thiol, malondialdehyde (MDA), and nitric oxide (NO) levels were investigated in rat blood serum using the spectrophotometric method. Oxidative Stress Index (OSI) was calculated by dividing TOC by TAC. Total bilirubin was measured with the colorimetric method using an ELISA kit. Liver tissues were stained with hematoxylin–eosin (HE) for histopathological examination. The difference in serum levels of TAC, TOC, OSI, PON, MDA, and thiol was statistically significant between the groups (P&lt;0.05). The difference in serum levels of NO and total bilirubin was not statistically significant between the groups (P&gt;0.05). The analysis of histopathological findings revealed uncommon mild hydropic degeneration in the MSG group and almost normal histological appearance in the MSG+Betanin group. This study demonstrated that betanin could increase the antioxidant effect and reduce the histopathological damage caused by MSG.

Clinico-Pathological Alterations and Therapeutic Management of Thiram Poisoning in Cattle

As there is very scarce literature on fungicide poisoning in livestock animals and in view of reporting fungicide poisoning in cattle in the study area, the present study was conducted to study the clinico-pathology of thiram poisoning in cattle and to standardize the therapeutic regime for the poisoning cases. Clinical cases suspected for Thiram poisoning on the basis of confirm evidence from animal owner were subjected to clinical examination, hematology and therapeutic management. Cases died of severe poisoning were subjected to post-mortem examination. A total of 17 cattle suspected for Thiram poisoning on the basis of history and evidence showed clinical signs of sudden onset of anorexia, salivation, shivering, teeth grinding, restlessness, prolonged sitting, tympany, colic, dyspnea and constipation or diarrhea in few cases. Significant increase in heart rate and respiration rate was observed while hematological analysis showed non-significant changes compared to healthy counterparts. Post-mortem and histopathological examination of cattle died of thiram poisoning showed mild hepatocellular degeneration, tubular necrosis in kidneys with focal infiltrates while marked edema and congestion was evident in lung tissues. The ailing cattle were treated with fluid therapy, anti-inflammatory drugs, vitamin B complex, atropine sulphate, antihistaminics along with laxative and prebiotics-probiotics showed good response to treatment with complete clinical recovery in 4-5 days of treatment. Being there is no specific antidote, the cases of fungicide like Thiram poisoning could be managed with symptomatic treatment and regular clinical assessment of the severity of the poisoning.

Non-linear Effect of Preexisting Cranial Adjacent Disc Degeneration on Cumulative 12-year Revision Risk Following Lumbar Fusions.

Retrospective analysis of prospectively collected data. To evaluate how preexisting adjacent segment degeneration status impacts revision risk for adjacent segment disease (ASD) after lumbar fusions. ASD incurs late reoperations after lumbar fusion surgeries. ASD pathogenesis is multifactorial. Preexisting adjacent segment degeneration measured by Pfirrmann is suggested as one of the predisposing factors. We sought to find deeper insights into this association by using a more granular degeneration measure, the Combined imaging score (CIS). A total of 197 consecutive lumbar fusions for degenerative pathologies were enrolled in a prospective follow-up (median 12 years). Preoperative cranial adjacent segment degeneration status was determined using Pfirrmann and CIS, which utilizes both radiographs and magnetic resonance imaging. Based on CIS, patients were trichotomized into tertiles (CIS <7, CIS 7-10, and CIS >10). The cumulative ASD revision risk was determined for each tertile. After adjusting for age, sex, body mass index, sacral fixation, and fusion length, hazard ratios (95% confidence intervals, CI) for ASD revisions were determined for each Pfirrmann and CIS score. Patients in the intermediate CIS tertile had a cumulative ASD revision risk of 25.4% (17.0% to 37.0%), while both milder degeneration (CIS <7) [13.2% (6.5% to 25.8%)] and end-stage degeneration (CIS >10) [13.6% (7.0% to 25.5%)] appeared to be protective against surgical ASD. Pfirrmann failed to show a significant association with ASD revision risk. Adjusted analysis of CIS suggested increased ASD revisions after CIS 7, which turned contrariwise after CIS 10. The effect of preexisting adjacent segment degeneration on ASD reoperation risk is not linear. The risk seems to increase with advancing degeneration but diminish with end-stage degeneration. Therefore, end-stage degenerative segments may be considered to be excluded from fusion constructs. Therapeutic Level III.

Genetic and clinical characteristics of PROM1-related retinal degeneration in Korean

This scientific report aims to comprehensively describe the genetic and clinical characteristics of PROM1-related retinal degeneration in Korean patients. Medical records of patients diagnosed with retinal dystrophy who underwent comprehensive ophthalmologic examination and genetic testing at Samsung Medical Center between January 2016 and April 2023 were retrospectively reviewed. Genetic testing included targeted gene panel sequencing and Sanger sequencing, with diagnosis based on the presence of a “Likely Pathogenic” or “Pathogenic Variant” in the PROM1 gene, as determined by the ACMG criteria. The study identified seven patients from five unrelated families with PROM1-related retinal degeneration, all carrying the autosomal dominant variant PROM1 p.R373C; no other PROM1 gene variants were detected. All patients exhibited degenerative retinal area within the macula, with peripheral retinal degeneration observed in five patients. Substantial interfamilial and intrafamilial variability was observed in the extent of macular and peripheral degeneration. Ultra-widefield autofluorescence imaging and fluorescein angiography aided in the detection of mild peripheral degeneration in one case. In conclusion, the autosomal dominant variant PROM1 p.R373C constitutes a significant proportion of PROM1-related retinal degeneration cases in the Korean population. The observed clinical heterogeneity may suggests the potential influence of additional genetic, epigenetic, and environmental factors on disease phenotypes.

Comparative histopathological analysis of age-associated intervertebral disc degeneration in CD-1 and C57BL/6 mice: Anatomical and sex-based differences.

Intervertebral disc (IVD) degeneration is a major contributor to back pain and disability. The cause of IVD degeneration is multifactorial, with no disease-modifying treatments. Mouse models are commonly used to study IVD degeneration; however, the effects of anatomical location, strain, and sex on the progression of age-associated degeneration are poorly understood. A longitudinal study was conducted to characterize age-, anatomical-, and sex-specific differences in IVD degeneration in two commonly used strains of mice, C57BL/6 and CD-1. Histopathological evaluation of the cervical, thoracic, lumbar, and caudal regions of mice at 6, 12, 20, and 24 months of age was conducted by two blinded observers at each IVD for the nucleus pulposus (NP), annulus fibrosus (AF), and the NP/AF boundary compartments, enabling analysis of scores by tissue compartment, summed scores for each IVD, or averaged scores for each anatomical region. C57BL/6 mice displayed mild IVD degeneration until 24 months of age; at this point, the lumbar spine demonstrated the most degeneration compared to other regions. Degeneration was detected earlier in the CD-1 mice (20 months of age) in both the thoracic and lumbar spine. In CD-1 mice, moderate to severe degeneration was noted in the cervical spine at all time points assessed. In both strains, age-associated IVD degeneration in the thoracic and lumbar spine was associated with increased histopathological scores in all IVD compartments. In both strains, minimal degeneration was detected in caudal IVDs out to 24 months of age. Both C57BL/6 and CD-1 mice displayed sex-specific differences in the presentation and progression of age-associated IVD degeneration. These results showed that the progression and severity of age-associated degeneration in mouse models is associated with marked differences based on anatomical region, sex, and strain. This information provides a fundamental baseline characterization for users of mouse models to enable effective and appropriate experimental design, interpretation, and comparison between studies.

Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls

ObjectiveTo gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA). MethodWe obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n ​= ​12), mild signs of joint damage (n ​= ​13) and end-stage OA (n ​= ​12). The protein profile was analysed by nano-liquid chromatography-mass spectrometry using data-independent acquisition and quantified by Spectronaut. Linear-mixed effects modelling was applied to extract the between-group comparisons. ResultsA similar protein profile was observed for the mild group as compared to healthy controls while the most different group was end-stage OA mainly for the medial compartment. When a pattern of gradual change in protein levels from healthy to end-stage OA was required, a 42-proteins panel was identified, suggesting a potential role in OA development. The levels of QSOX1 were lower and G6PD higher in the mild group following the proposed protein abundance pattern. Qualitative protein changes suggest lower levels of CYTL1 as a potential biomarker of early joint degradation. ConclusionFor future targeted proteomic approaches, we propose a candidate panel of 42 proteins based on gradually altered meniscal posterior horn protein abundance patterns associated with joint degradation.