Perceptions of COVID-19 during and after the Omicron outbreak among healthcare personnel in Indonesia.

Introduction: The COVID-19 pandemic occurred in several waves with different levels of seriousness. Healthcare personnel (HCP) constituted a high-risk population for COVID-19, necessitating monitoring of their knowledge, attitudes, and practices (KAP) status and level of psychological distress. This study investigated differences in the impacts of COVID-19 during and after the Omicron outbreak among HCP in Indonesia. Methods: An online structured questionnaire survey was distributed twice in selected hospitals of Indonesia: the first survey was between December 2021 and February 2022 (Omicron era) and the second between August and October 2022 (post-Omicron era). A multiple logistic regression model was used to determine the differences in KAP and psychological distress among HCP toward COVID-19 with demographic characteristics adjusted for. Results: This study included 402 (Omicron era) and 584 (post-Omicron era) HCP members. Positive attitudes were more common in the Omicron era than in the post-Omicron era (p = 0.001). The availability of face shields and protective eyewear significantly decreased from 62.7 to 55.6% (p = 0.028). However, psychological distress among HCP significantly increased after the Omicron outbreak (p = 0.024). Multiple logistic regression analyses revealed a decrease of positive attitudes (OR = 0.626; 95% CI = 0.476-0.823) in the post-Omicron era. Conclusion: Our data indicated a significant increase in psychological distress among HCP in the post-Omicron era. These findings suggest a need for greater focus on psychological distress among HCP in Indonesia.

Clerodendrum wallichii Merr Methanol Extract Protected Alcohol-Induced Liver Injury in Sprague-Dawley Rats by Modulating Antioxidant Enzymes.

Materials and Methods: An oral acute toxicity study was carried out following OECD guidelines. Hepatotoxicity was induced by the administration of ethanol for 4 weeks. Hepatic enzymes and oxidative stress biomarkers were determined using commercial diagnostic kits. Results: Treatment of rats with MECW (800 mg/kg) showed the highest reduction of body weight (4.76 ± 0.372 vs. 16.92 ± 0.846) and liver weight (3.06 ± 0.128 vs 5.55 ± 0.311). Treatment of rats with MECW at 200, 400, 600, 800, and 1000 mg/kg significantly ( ∗∗ p < 0.01) reduced SGPT. Similarly, serum SGOT and ALP were significantly decreased by MECW (200, 400, 600, 800, and 1000 mg/kg). All used doses of MECW significantly increased antioxidant enzymes GSH and SOD. MECW (600 and 800 mg/kg) significantly promoted CAT levels in liver tissues; whereas, it significantly diminished oxidative biomarker, MDA. Histopathological observations of the liver showed improvement in the architecture of hepatic cells having signs of protection with a reduced number of inflammatory cells, vascular degeneration and congestion, cellular degeneration, necrosis, and significant reduction of fatty cells accumulation. Acute toxicity study resulted in the well-tolerability and safety of used doses of MECW (200-1000 mg/kg) in rats. Conclusion: Our study clearly demonstrated the hepatoprotective effect of Clerodendrum wallichii extract against ethanol-induced liver injury in the laboratory rats model.

Global geographical discrepancy in numerical distribution of cardiovascular surgeries and human resource development in South Asia.

Objective: The region South Asia is in the south-central part of the Asian continent. The 8 countries of the area, Afghanistan, Bangladesh, Bhutan, India, Nepal, The Maldives, Pakistan, and Sri Lanka collectively possess 1.8 billion people living in 5.1 million square miles. Covering 2.96% of World's surface, this area is inhabited by 23.9% of the world population. The objective of this study was to observe the number of cardiac operations in South Asia and the human resource development facilities of cardiac surgery in the region. Methods: Information was collected from the surgeons and anesthetists through personal visits, phone calls, and emails. The websites of various organizations were also checked. Results: The estimated number of cardiac operations collectively performed in the South Asian countries was between 250,000 and 300,000 as of 2019. With more than 6 times the US population, these nations combined performed less than half of the annual number of cardiac operations performed in the United States. The number of operations per million population ranged from 62 to 271 in different countries. This indicates that there should be more capacity-building of surgeons to meet the growing demand of operations. India, Pakistan, Bangladesh, Sri Lanka, and Nepal have their own education and training systems for cardiovascular surgeons. A substantial portion of the seats available for cardiovascular surgery courses remained vacant in South Asia these days. Conclusions: Five countries have their various surgical education and training programs. There should be coordinated efforts to increase the production of new cardiac surgeons in the region.

A candidate gene of Alzheimer diseases was mutated in senescence-accelerated mouse prone (SAMP) 8 mice.

The senescence-accelerated mouse prone (SAMP) 8 strain exhibits age-related learning and memory deficits (LMD) at 2 months of age. We have found strong association of chromosome 12 locus with learning memory deficit (LMD) phenotype in SAMP8 strain. In the course of searching candidate gene, here we identified solute carrier family 24 sodium/potassium/calcium exchanger member 4 (Slc24a4) in SAMP8 chromosome 12 LMD possessing one single nucleotide polymorphism causing amino acid replacement of Threonine at 413 position with Methionine. Since SLC24A4 has been postulated as a candidate of late onset Alzheimer's diseases (LOAD), we further analyze the functional importance of this polymorphism. By expressing Slc24a4 protein in HEK293 cells, here we showed polymorphic SAMP8 type Slc24a4-T413 M causing significant loss of calcium ion (Ca2+) transporter activity in cells compared with that of wild type mouse (Slc24a4-WT). However, no study yet shows any functional association of human SLC24A4 polymorphism with the onset of LOAD pathogenesis. Thus, our present finding may further help to clarify the importance of this ion exchanger with age related cognitive dysfunction.

Polymorphic SERPINA3-R124C reduces pathogenesis of its wild type by shortening the lifetime of oligomeric Aß.

Amyloid beta (Aß) 42 peptide accumulated in Alzheimer disease (AD) patients' brain, often colocalized with serine protease inhibitor family A member 3 (SERPINA3). Being a chaperon, SERPINA3 accelerated Aß42 fibrillization. While analyzing chaperon activity of human SERPINA3 polymorphisms, we found SERPINA3-R124C played a role in protecting cells from Aß42 cytotoxicity. SH-SY5Y cells exposed to Aß42 preincubated with wild-type SERPINA3 (SERPINA3-WT) resulted in extended toxicity leading cell death whereas Aß42 with SERPINA3-R124C resulted in less cytotoxicity. Transmission electron microscope and thioflavin T assay revealed that SERPINA3-R124C shortened lifetime of small soluble oligomer and maintained ß-sheet rich protofibril-like aggregates for longer time compared to that of with SERPINA3-WT. Western blot assay confirmed that SERPINA3-R124C converted Aß42 mostly into high molecular aggregates. Here, we demonstrate first time that polymorphic SERPINA3 acts as a benign chaperon by modulating the transition states of Aß42, which may contribute to the reduction of AD risk.

Surgical Treatment of Atrial Myxomas: Outstanding Outcome of a Treacherous Tumor.

BACKGROUND: Primary cardiac tumors are quite rare and mostly benign in nature. Most of the benign heart tumors are myxomas. These might present with a wide range of symptoms from being completely asymptomatic to having life-threatening complications like stroke, heart failure, or even sudden death. This study summarizes our 6-year clinical experience with surgical resection of cardiac tumors at Chittagong Medical College and Hospital, Chattogram, Bangladesh. METHODS: Twenty patients who underwent surgical excision of primary intracardiac myxoma between February 2014 and February 2020 were included in the study. Seventeen (85%) of them were female and 3 (15%) were male. Mean age was 43.4 ± 14.1 years. The tumors were located in the left atrium in 19 patients and in 1 patient it was in the right atrium. The most common attachment site was the interatrial septum. Most of the patients presented with dyspnea. Preoperative diagnosis was established using transthoracic echocardiography with colour Doppler. Surgery for all patients was via median sternotomy. RESULTS: All 20 patients survived the surgery. Mean tumor dimension was 4.6 ± 3.5 cm in the longest diameter. Solid tumors were detected in 13 patients (65%) whereas papillary myxomas were found in 7 patients (35%). On follow-up of these 20 patients, there was no perioperative death. One patient presented with recurrence 28 months after the surgery. CONCLUSIONS: Although cardiac myxomas carry the risk of serious systemic and cardiac symptoms, prompt surgical excision gives excellent outcome.

INTRODUCTION: Les tumeurs cardiaques primitives sont assez rares et pour la plupart bénignes par nature. La plupart des tumeurs cardiaques bénignes sont des myxomes, qui pourraient se manifester sous diverses formes allant de l'absence complète de symptômes à des complications mettant la vie en danger telles que les accidents vasculaires cérébraux, l'insuffisance cardiaque, voire la mort subite. La présente étude résume les six années d'expérience clinique en résection chirurgicale de tumeurs cardiaques au Chittagong Medical College and Hospital, Chattogram, Bangladesh. MÉTHODES: Vingt patients qui avaient subi une excision chirurgicale d'un myxome intracardiaque primitif entre février 2014 et février 2020 ont fait partie de l'étude. Dix-sept (85 %) étaient des femmes, et trois (15 %), des hommes. L'âge moyen était de 43,4 ± 14,1 ans. Dix-neuf patients avaient une tumeur située dans l'atrium gauche, et un patient avait une tumeur située dans l'atrium droit. Le site de fixation le plus fréquent était le septum interauriculaire. La plupart des patients accusaient une dyspnée. Le diagnostic préopératoire était établi par échocardiographie Doppler couleur transthoracique. Tous les patients opérés ont subi une sternotomie médiane. RÉSULTATS: Les 20 patients ont survécu à l'intervention chirurgicale. La dimension moyenne de la tumeur était de 4,6 ± 3,5 cm dans le plus grand diamètre. Treize (65 %) patients avaient des tumeurs solides, et sept (35 %) patients, des myxomes papillaires. Aucun décès périopératoire n'a été observé durant le suivi de ces 20 patients. Un patient a eu une récidive 28 mois après l'intervention chirurgicale. CONCLUSIONS: Bien que les myxomes cardiaques comportent un risque de symptômes systémiques et cardiaques sérieux, l'excision chirurgicale rapide apporte d'excellents résultats.

Polymorphic SERPINA3 prolongs oligomeric state of amyloid beta.

Molecular chaperon SERPINA3 colocalizes with accumulated amyloid peptide in Alzheimer's disease (AD) patient's brain. From the QTL analysis, we narrowed down Serpina3 with two SNPs in senescence-accelerated mouse prone (SAMP) 8 strain. Our study showed SAMP8 type Serpina3 prolonged retention of oligomeric Aß 42 for longer duration (72 hr) while observing under transmission electron microscope (TEM). From Western blot results, we confirmed presence of Aß 42 oligomeric forms (trimers, tetramers) were maintained for longer duration only in the presences of SAMP8 type Serpina3. Using SH-SY5Y neuroblastoma cell line, we observed until 36 hr preincubated Aß 42 with SAMP8 type Serpina3 caused neuronal cell death compared to 12 hr preincubated Aß 42 with SAMR1 or JF1 type Serpina3 proteins. Similar results were found by extending this study to analyze the effect of polymorphism of SERPINA3 gene of the Japanese SNP database for geriatric research (JG-SNP). We observed that polymorphic SERPINA3 I308T (rs142398813) prolonged toxic oligomeric Aß 42 forms till 48 hr in comparison to the presence wild type SERPINA3 protein, resulting neuronal cell death. From this study, we first clarified pathogenic regulatory role of polymorphic SERPINA3 in neurodegeneration.

Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms.

Inorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P = 0.028), nail (529.29 ± 38.76 ppb, P < 0.05) and cardiac tissue (4.83 ± 0.50 ppb, P < 0.05) samples. Patients' age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017-8.012, P = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032-3.249, P = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients' disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA (P = 0.012) and AG (P = 0.034) genotypes and cardiac iAs concentration with AA (P = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280-138.845, P = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065-310.757, P = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325-108.674, P = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280-138.845, P = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.

Expression and function of FGF9 in the hypertrophied ligamentum flavum of lumbar spinal stenosis patients.

BACKGROUND CONTEXT: Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF. PURPOSE: To evaluate FGF9 expression and function in human LF with and without hypertrophy. STUDY DESIGN: This study employed a basic research study design utilizing human LF tissue for histological analyses. PATIENT SAMPLES: Hypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery. METHODS: LF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF. RESULTS: Histological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients' age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells. CONCLUSION: The present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration. CLINICAL SIGNIFICANCE: The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.

Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction.

Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p < 0.001) inhibited gastric lesions and malondealdehyde (MDA) levels and upregulated antioxidant enzymes level. Furthermore, nine compounds were documented as bioactive, displayed good binding affinities to against gastric H+-K+ATPase enzyme while these compounds illustrated inhibitory effect. From these studies, it is established MEBLL has ulcer healing property as unveiled by in vivo and in silico studies.

Long-term, Time-course Evaluation of Ligamentum Flavum Hypertrophy Induced by Mechanical Stress: An Experimental Animal Study.

STUDY DESIGN: Experimental animal study. OBJECTIVE: The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model. SUMMARY OF BACKGROUND DATA: LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated. METHODS: Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2-3 and L4-5 posterolateral fusion and resection of the L3-4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3-4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts. RESULTS: In the mechanical stress group, LFs at the L3-4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group. CONCLUSION: We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.Level of Evidence: SSSSS.

Can Conventional Magnetic Resonance Imaging Substitute Three-Dimensional Magnetic Resonance Imaging in the Diagnosis of Lumbar Foraminal Stenosis?

STUDY DESIGN: Retrospective radiological comparative design. PURPOSE: To investigate whether conventional magnetic resonance imaging (MRI) could substitute three-dimensional (3D)-MRI for the calculation of the foraminal stenotic ratio (FSR) and clarification of which patients can be assessed more accurately using 3D-MRI. OVERVIEW OF LITERATURE: Previous studies have indicated that 3D-MRI is useful for diagnosing lumbar foraminal stenosis. The FSR obtained using 3D-MRI, described as the ratio of stenosis length, characterized by perineural fat obliteration, to the length of the entire foramen, could indicate the stenosis severity; however, this method is time-consuming and expensive. The FSR also can be calculated using conventional MRI. METHODS: We investigated 154 foramina at L5-S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. RESULTS: In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. CONCLUSIONS: FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.

Can Conventional Magnetic Resonance Imaging Substitute Three-Dimensional Magnetic Resonance Imaging in the Diagnosis of Lumbar Foraminal Stenosis?

Methods@#We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. @*Results@#In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. @*Conclusions@#FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.

Can Conventional Magnetic Resonance Imaging Substitute Three-Dimensional Magnetic Resonance Imaging in the Diagnosis of Lumbar Foraminal Stenosis?

Methods@#We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. @*Results@#In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. @*Conclusions@#FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.

Increased advanced glycation end products in hypertrophied ligamentum flavum of diabetes mellitus patients.

BACKGROUND CONTEXT: Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). Although LSS prevalence is known to be higher in patients with diabetes mellitus (DM), the underlying pathomechanisms are not well understood. Abnormal advanced glycation end products (AGEs) formation occurs in DM and promotes tissue damage in various organs through degeneration and inflammation. PURPOSE: To analyze and compare LF histology focused on AGE status between control patients, LSS patients with DM, and LSS patients without DM. STUDY DESIGN/SETTING: Basic research study design utilizing human LF tissue for histologic analyses. PATIENT SAMPLE: LF tissue samples were collected from patients who underwent lumber decompression surgery for LSS in the author's institution. OUTCOME MEASURES: Quantitative visualization of Masson's Trichrome (MT) stains, and AGE immunohistochemistry (IHC) for the three groups. METHODS: Ten LF specimens from LSS patients with DM (DM group, mean age 71.4 years), 10 from LSS patients without DM (non-DM group, mean age 71.2 years), and 9 from patients with lumbar disc herniation or cauda equina tumor (control group, mean age 49.0 years) were harvested during surgery and histologically analyzed. Percentage of elastic fiber areas (%EF) was measured with MT staining, and the percentage of AGE immuno-positive areas (%AGEs) was measured with IHC. RESULTS: The average %EFs were 12.8 in the DM group, 17.1 in the non-DM group, and 24.9 in the control group. The decrease in the elastic fibers was significantly more in the DM group than in the non-DM (p<.01) and control groups (p<.001). Accumulation of AGEs was found mainly in the extracellular matrix in areas of elastic fiber disruption. The %AGEs were 18.3 in the DM group, 12.1 in the non-DM group, and 4.6 in the control group. These were significantly larger in the DM group than in the non-DM (p<.01) and control (p<.01) groups. The %AGEs also positively correlated with patient age (p<.01, R=0.47). CONCLUSIONS: Accumulation of AGEs is significantly greater in the LF of DM patients and correlates with patient age. AGEs may accelerate degeneration and hypertrophy of LF with age and may lead to higher prevalence of LSS in patients with DM. CLINICAL SIGNIFICANCE: The present results partly reveal the molecular mechanism of LF hypertrophy, suggesting that AGEs may be involved in the process of LF degeneration in the elderly and patients with DM.

Fibroblast Growth Factor 9 Is Upregulated Upon Intervertebral Mechanical Stress-Induced Ligamentum Flavum Hypertrophy in a Rabbit Model.

STUDY DESIGN: Case-control study of an animal model. OBJECTIVE: To investigate the factors that are upregulated and potentially related to degenerative changes in the ligamentum flavum (LF) upon mechanical stress concentration. SUMMARY OF BACKGROUND DATA: LF hypertrophy is reported to be associated with mechanical stress. However, few studies, using exhaustive analysis with control subjects, on the molecular mechanisms of LF hypertrophy have been published. METHODS: Fourteen rabbits were used for this study. The first group underwent L2-3 and L4-5 posterolateral fusion with instrumentation and resection of the L3-4 supraspinal muscle to concentrate the mechanical stress on L3-4, whereas the other group underwent a sham operation. The deep layer of the LF from L2-3 to L4-5 in both groups was harvested after 16 weeks. Gene expression was evaluated exhaustively using DNA microarray and real-time polymerase chain reaction (RT-PCR). Fibroblast growth factor 9 (FGF9) protein expression was subsequently examined by immunohistological staining. RESULTS: A total of 680 genes were found to be upregulated upon mechanical stress concentration and downregulated upon mechanical shielding compared with those in the sham group. Functional annotation analysis revealed that these genes not only included those related to the extracellular matrix but also those related to certain FGF families. On RT-PCR validation and immunohistological analysis, we identified that the FGF9 protein increases in the LF upon mechanical stress, especially in the area wherein degenerative changes were frequently identified in the previous literature. CONCLUSION: FGF9 and its pathway are suggested to contribute to the degenerative changes in the LF following mechanical stress. This finding will be helpful in further understanding the molecular mechanism of human LF degeneration. LEVEL OF EVIDENCE: N/A.

Nephrocutaneous Fistula due to Xanthogranulomatous Pyelonephritis.

While the development of a fistulous tract from the kidney to the proximal adjacent organs is relatively common, a tract leading to the skin is a rare occurrence. The primary cause of a fistula is prior surgical intervention or malignancy leading to abscess formation. Our case involves Xanthogranulomatous pyelonephritis (XGP) causing a longstanding lobulated abscess, ultimately leading to the formation of a fistulous tract.

Non-insidious Large Joint Manifestation of Severe Cachectic Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder in which constitutional symptoms typically occur before joint swelling becomes a true clinical phenomenon. Weight loss, although common, is generally mild in nature and occurs after long standing inflammation. While large joints do become inflamed, RA has a much stronger predilection for the small joints. Our case is a rarity in the fact that there was initial large joint swelling without long standing inflammation. Additionally, the weight loss was cachectic in nature and extreme. Furthermore, while extra-articular manifestations do commonly occur, spontaneous pneumothorax is certainly atypical. The content of this manuscript serves to enlighten hospitalist physicians and residents, as to the odd way in which a case like this may present.

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways.

Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the main pathomechanism of LSS, but the reason for its occurrence is not clearly elucidated. In this study, we established a novel animal model of intervertebral mechanical stress concentration and investigated the biological property of the LF. The LF with mechanical stress concentration showed degeneration with elastic fibres disruption and cartilage matrix increase, which are similar to the findings in hypertrophied LF from patients with LSS. By contrast, decreased Col2a1 expression was found in the LF at fixed levels, in which mechanical stress was strongly reduced. These findings indicate that mechanical stress plays a crucial role in LF hypertrophy through cartilage matrix increase. The findings also suggest that fusion surgery, which eliminates intervertebral instability, may change the property of the LF and lead to the relief of patients' symptoms.