Role of mitochondrial sirtuins in rheumatoid arthritis.

AIM: Current study is intended to evaluate the expression and epigenetic variations of mitochondrial situins in 306 rheumatoid arthritis (RA) cases and compared with age/gender matched controls. MATERIALS AND METHODS: The expression level was measured using the quantitative Real time PCR (qPCR) and epigenetic analysis was performed by measuring deacetylation activity. Oxidative stress was also measured in present study using the enzyme linked immunoassay (ELISA). The obtained results were evaluated by means of the student t-test, spearman correlation and ROC curve analysis. RESULTS: Expression analysis showed the significant downregulation of SIRT3 (p < 0.0001), SIRT4 (p < 0.0001) and SIRT5 (p < 0.0001) in RA cases when compared with controls. Downregulation of mitochondrial sirtuins was significantly associated with positive anti-CCP status, increased ESR level and with increased CRP levels. Epigenetic analysis showed significant increased histone deacetylation in RA patients compared to controls. Co-expression analysis showed the significant negative association between expression level of mitochondrial sirtuins and deacytylation level (SIRT3 r = -0.438, p < 0.0001; SIRT4 r = -0.424, p < 0.0001; SIRT5 r = -0.282, p < 0.0001). ROC curve analysis exhibited that downregulation of mitochondrial sirtuins (SIRT3 AUC = 0.91, p < 0.001; SIRT4 AUC = 0.92, p < 0.001; SIRT5 AUC = 0.85, p < 0.001) was act as the good diagnostic marker for detection/diagnosis of arthritis. CONCLUSIONS: The results show that significant deregulation of mitochondrial sirtuins was associated with increased arthritis risk and can be act as an indicator of advance clinical outcome.

Genetic and expression deregulation of immunoregulatory genes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases globally, and is an important public health concern, associating with early death and systemic complications. Although key development in RA treatment has already been made still RA affected individuals face comorbidity and disability. Therefore, there is a need to discover new risk factors in helping early diagnosis and treatment of RA. The present study is designed to assess the variations of Vitamin D receptor (VDR) and interleukin -6 (IL-6) in RA patients. Polymorphisms of said genes were calculated in 300 RA patients and 300 controls, using Tetra-ARMS polymerase chain reaction. Secondly, expression levels of selected genes were checked using the quantitative PCR (qPCR) and obtained results were evaluated using a different statistical test. Logistic regression analysis showed that frequency of mutant allele of VDR gene polymorphisms (rs11168268, OR = 4.84; 95% CI = 2.94-7.97; p = 0.0001; rs2248098, OR = 1.65; 95% CI = 1.07-2.54; p = 0.02) and IL-6 gene polymorphisms (rs184229712, OR = 2.47; 95% CI = 1.56-3.92, p = 0.0001; rs36215814, OR = 2.14; 95% CI = 1.30-3.53; p = 0.002) was observed significantly higher in RA patients vs controls. Expression analysis showed the significant upregulation of IL-6 (p < 0.0001) and downregulation of VDR gene (p < 0.0001) in RA cases vs controls. ROC curve analysis showed that downregulation of IL-6 (AUC = 0.86, p < 0.001) and upregulation of VDR (AUC = 0.77, p < 0.001) was act as the good diagnostic marker for detection/diagnosis of arthritis. In conclusions, data from the present study showed the significant involvement of VDR and IL-6 gene variations in RA pathogenesis.

Intra-articular distal radius fractures: Postoperative roentgenographic and functional outcomes.

OBJECTIVE: To assess the outcome of volarlocking compression plate fixation for intra-articular distal radius fractures with respect to function of hand and roentgenographic parameters. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised patients who underwent locking compression plate fixation for intra-articular distal radius fractures between June 2009 and July 2012. Case notes, radiographic assessment and functional outcomes were noted. Functional outcome was determined with the help of telephone-based quick-dash score questionnaire administered atleast 6 months post-surgery. Radiological assessment of radial inclination, radial height and volar tilt was measured on immediate postoperative radiographs and then again measured at last available follow-up which ranged from 4 to 116 weeks. RESULTS: The mean age of the 43 patients in the study was 47.31±14.24 years (range: 20-95 years) at the time of injury. Mean Quick Dash score at 6-month follow-up was 17.2±8.8 (range: 4-40). The outcome was very good in 1(2.2%), good in 30(66.7%), satisfactory in 10(22.2%) and poor in 4(8.9%) patients. Mean immediate postoperative radial inclination, volar tilt and radial height were 17.26±3.23°, 7.6±3.87° and 10.2±1.95mm respectively. Corresponding values at the last follow-up were 17±3.89°, 7.67±4.28° and 9.8±1.8mm. CONCLUSIONS: Use of locking compression plate for intra-articular distal radius fracture showed good results comparable with global literature.

Management of Cyclops Syndrome: A case report.

Anterior Cruciate ligament (ACL) is a typical athletic injury. One of the most frequent complication after ACL reconstruction is reduced range of motion (ROM) due to the impingement on the inter-condylar notch of a fibrous tissue mass, defined as Cyclops Syndrome. We report the case of a 25 years old male, who underwent reconstruction of ACL with Gracilis-semitendinosus (GR-ST) tendons with delayed onset of loss of knee extension seven years after ACL reconstruction. Clinical and magnetic resonance image (MRI) findings were consistent with Cyclops syndrome. The patient underwent arthroscopy in May 2015, which revealed a fixed fibrous nodule impinging on the inter-condylar notch in extension that was treated by mechanical shaving, radiofrequency ablation remodeling inter-condylar notch and releasing of the ACL transplant. After surgery our patient returned to his routine activities after 5 days and started running about 10 days later, without anterior knee pain and without deficit of hyperextension.

Synergistic effects of ß-NaFeO2 ferrite nanoparticles for photocatalytic degradation, antibacterial, and antioxidant applications.

Here, synthesis and thorough characterization of ß-NaFeO2 nanoparticles utilizing a co-precipitation technique is presented. XRD analysis confirmed a hexagonal-phase structure of ß-NaFeO2. SEM revealed well-dispersed spherical nanoparticles with an average diameter of 45 nm. The FTIR spectrum analysis revealed weak adsorption bands at 1054 cm-1 suggested metal-metal bond stretching (Fe-Na). UV-Visible spectroscopy indicates a 4.4 eV optical band gap. Colloidal stability of ß-NaFeO2 was evidenced via Zeta potential (-28.5 mV) and Dynamic Light Scattering (DLS) measurements. BET analysis reveals a substantial 343.27 m2 g-1 surface area with mesoporous characteristics. Antioxidant analysis indicates efficacy comparable to standard antioxidants, while concentration-dependent antibacterial effects suggest enhanced efficacy against Gram-positive bacteria, particularly Streptococcus. The Photocatalytic activity of ß-NaFeO2 showed significant pollutant degradation (>90% efficiency), with increased degradation rates at higher nanoparticle concentrations, indicating potential for environmental remediation applications.

Cobalt Iron Oxide (CoFe2O4) Nanoparticles Induced Toxicity in Rabbits.

The market for nanoparticles has grown significantly over the past few decades due to a number of unique qualities, including antibacterial capabilities. It is still unclear how nanoparticle toxicity works. In order to ascertain the toxicity of synthetic cobalt iron oxide (CoFe2O4) nanoparticles (CIONPs) in rabbits, this study was carried out. Sixteen rabbits in total were purchased from the neighborhood market and divided into two groups (A and B), each of which contained eight rabbits. The CIONPs were synthesized by the co-precipitation method. Crystallinity and phase identification were confirmed by X-ray diffraction (XRD). The average size of the nanoparticles (13.2 nm) was calculated by Scherrer formula (Dhkl = 0.9 λ/ß cos θ) and confirmed by TEM images. The saturation magnetization, 50.1 emug-1, was measured by vibrating sample magnetometer (VSM). CIONPs were investigated as contrast agents (CA) for magnetic resonance images (MRI). The relaxivity (r = 1/T) of the MRI was also investigated at a field strength of 0.35 T (Tesla), and the ratio r2/r1 for the CIONPs contrast agent was 6.63. The CIONPs were administrated intravenously into the rabbits through the ear vein. Blood was collected at days 5 and 10 post-exposure for hematological and serum biochemistry analyses. The intensities of the signal experienced by CA with CIONPs were 1427 for the liver and 1702 for the spleen. The treated group showed significantly lower hematological parameters, but significantly higher total white blood cell counts and neutrophils. The results of the serum biochemistry analyses showed significantly higher and lower quantities of different serum biochemical parameters in the treated rabbits at day 10 of the trial. At the microscopic level, different histological ailments were observed in the visceral organs of treated rabbits, including the liver, kidneys, spleen, heart, and brain. In conclusion, the results revealed that cobalt iron oxide (CoFe2O4) nanoparticles induced toxicity via alterations in multiple tissues of rabbits.

Vitamin D deficiency in dengue fever patients' coinfected with H. pylori in Pakistan. A case-control study.

Introduction: Dengue fever is a vector-borne disease with an estimate of 390 million persons getting the infection each year with a significant public health impact. It has been reported DENV patients with vitamin D deficiency led to severe form of dengue infection; while H. pylori coinfection alters vitamin D receptors leading to vitamin D deficiency. We hypothesize that DENV patient's having low vitamin D along with H. pylori coinfection could have worsen dengue severity as well as vitamin D deficiency. In this case-control study, we compared (I) the vitamin D deficiency in dengue fever cases with or without H. pylori coinfection, and (II) negative dengue fever as a control with or without H. pylori coinfection. We have also assessed the correlation between vitamin D levels and its effect on warning signs of the dengue fever. Further, we have investigated whether coinfection with H. pylori has any effect on warning signs in the dengue fever patients and the vitamin D deficiency in all serotypes of the dengue virus infected patients. Methods: In this case control study the association of the vitamin D levels with age, gender and H. pylori coinfection in dengue fever hospitalized patients was assessed using chi-square and multivariate logistic regression analysis. Results: Four hundred dengue fever patients with H. pylori coinfection were compared with 400 dengue negative controls with H. pylori coinfection. The mean age was 29.96 ± 10.5 and 29.88 ± 10.7 years among cases and controls, respectively. Most dengue fever patients with H. pylori coinfection were deficient in vitamin D compared with negative dengue controls with H. pylori coinfection. In multivariate logistic regression, the dengue cases with H. pylori coinfection were.056 times (95% CI: 0.024, 0.128, P = 0.000) more likely to have vitamin D "deficiency', while compared with the cases who did not have H. pylori coinfection. Conclusion: The present study proposes that vitamin D deficiency in dengue fever patients coinfected with H. pylori is much higher than the dengue fever negative controls coinfected with H. pylori. As hypothesized the DENV patient with H. pylori coinfection has vitamin D deficiency as well as increased dengue severity.

Hematobiochemical, Oxidative Stress, and Histopathological Mediated Toxicity Induced by Nickel Ferrite (NiFe2O4) Nanoparticles in Rabbits.

From the past few decades, attention towards the biological evaluation of nanoparticles (NPs) has increased due to the persistent and extensive application of NPs in various fields, including biomedical science, modern industry, magnetic resonance imaging, and the construction of sensors. Therefore, in the current study, magnetic nickel ferrite (NiFe2O4) nanoparticles (NFNPs) were synthesized and evaluated for their possible adverse effects in rabbits. The crystallinity of the synthesized NFNPs was confirmed using X-ray diffraction (XRD) technique. The saturation magnetization (46.7 emug-1) was measured using vibrating sample magnetometer (VSM) and 0.35-tesla magnetron by magnetic resonance imaging (MRI). The adverse effects of NFNPs on blood biochemistry and histoarchitecture of the liver, kidneys, spleen, brain, and heart of the rabbits were determined. A total of sixteen adult rabbits, healthy and free from any apparent infection, were blindly placed in two groups. The rabbits in group A served as control, while the rabbits in group B received a single dose (via ear vein) of NFNPs for ten days. The blood and visceral tissues were collected from each rabbit at days 5 and 10 of posttreatment. The results on blood and serum biochemistry profile indicated significant variation in hematological and serum biomarkers in NFNP-treated rabbits. The results showed an increased quantity of oxidative stress and depletion of antioxidant enzymes in treated rabbits. Various serum biochemical tests exhibited significantly higher concentrations of different liver function tests, kidney function tests, and cardiac biomarkers. Histopathologically, the liver showed congestion, edema, atrophy, and degeneration of hepatocytes. The kidneys exhibited hemorrhages, atrophy of renal tubule, degeneration, and necrosis of renal tubules, whereas coagulative necrosis, neutrophilic infiltration, and severe myocarditis were seen in different sections of the heart. The brain of the treated rabbits revealed necrosis of neurons, neuron atrophy, and microgliosis. In conclusion, the current study results indicated that the highest concentration of NPs induced adverse effects on multiple tissues of the rabbits.

Characterization of sand fly breeding sites in district Malakand, Khyber Pakhtunkhwa, Pakistan, and evaluation of risk factors for cutaneous leishmaniasis in the region.

Present study was carried to determine the sand fly species composition, breeding sites ecology, seasonal abundance, and spatial distribution in district Malakand, Khyber Pakhtunkhwa, Pakistan. In addition, risk factors associated with cutaneous leishmaniasis (CL) were also evaluated. Survey of indoor and outdoor habitats was carried out using sticky traps in 31 villages of Dargai and Batkhela tehsils of Malakand. Soil from habitats of adult and immature sand flies was analysed. Questionnaire-based household survey was also performed in these villages to assess risk factors associated with CL. Soil samples from selected CL positive households were analysed for its contents. Additionally, clinicoepidemiological data from local health centres was examined for the year 2019. Total of 3,140 sand flies belonging to 18 species were collected. Phlebotomus sergenti was the most abundant species (38.16%). Its abundance had a strong positive correlation with mean monthly relative humidity and negative correlation with average temperature. Phlebotomus sergenti and Phlebotomus papatasi were abundant at an elevation ranging from 320 to 1,120 m above sea level and in agricultural lands near human settlements. Flight height preference apparatus collected maximum sand flies at 30 cm (1ft) above the ground and all species associated negatively with height. Soil analysis from habitats of adult and immature flies showed that highest mean number of adults and immatures were recorded from silt loam which carried highest concentrations of K2 O, Mg, Ca, and Zn. Number of immature sand flies correlated moderately (r = .7, p < .05) with K2 O soil concentrations. There was significant similarity between organic matter contents in soil samples from positive breeding sites and CL households (Wilcoxon rank-sum test, p = .1976). In multivariate analysis model for CL risk factors, age (26-35 and >35 years), knowledge of leishmaniasis, living in a middle and upper class, preachers visit to villages, and assumption that Afghan refugees are more prone to CL were significant. CL patient's archived data from health centres showed that majority of patients had lesions on face and hands. Patient's influx was highest in February and March.

Efficacy of Oral Vitamin D3 Therapy in Patients Suffering from Diffuse Hair Loss (Telogen Effluvium).

The aim of the present study was to estimate the prevalence of telogen effluvium (TE) and to evaluate the efficacy of vitamin D in the treatment of this problem in women belonging to various cities of south Punjab, Pakistan. In the present study, 40 adult women suffering from the problem of TE were included. Each woman was treated with oral vitamin D3 (200,000 IU) therapy fortnightly and a total of 6 doses were given to each patient. After 15 d of the last dose, the condition of patients was assessed clinically. The mean age of female patients was 32.2±1.5 y, 42.5% of the patients between 21-30 y of age were found to be more frequently affected with TE compared to 35% females of 31-40 y of age. Results showed significant improvement in hair growth in young (r=0.457 p<0.003) women and in those, which do not use sunscreen (r=-0.331 p<0.037) but commonly utilize milk or milk protein (r=-0.311 p<0.051). Vitamin D3 therapy resulted in the improvement of the condition in 82.5% (p<0.001) patients of TE. The use of oral vitamin D3 (200,000 IU, fortnightly) for 3 mo resulted in significant improvement in hair regrowth in the patient of TE. Results showed improvement in hair growth in young women those do not use sunscreen but commonly utilize milk or milk protein.

Eradication of advanced pelvic hydatid bone disease after limb salvage surgery - 5-year follow-up: a case report.

INTRODUCTION: Echinococcosis is produced by the larval stage of Echinococcus granulosus; it is a parasitic disease which is seen rarely in humans and has adverse outcomes. We report a case of advanced pelvic hydatid bone disease with successful limb salvage surgery. Our patient had a 5-year follow-up without recurrence which is a rarity as per the literature. Early diagnosis and prompt medical therapy are necessary for effective management whereas delayed diagnosis is always fraught with the risk of recurrence and sepsis. CASE PRESENTATION: In 2009, a 30-year-old woman, native of Karachi (Sindhi ethnicity), presented at our clinic with history of a pathological fracture 11 years earlier. Her fracture was initially misdiagnosed and fixed. Subsequently she had persistent disease that progressed with time. Following this she underwent multiple surgeries and the diagnosis of hydatid disease was made but despite multiple debridements and medical therapy she was not cured and finally she was offered a hemipelvectomy (limb sacrifice). On presentation to our hospital she was counseled regarding options of hemipelvectomy versus a limb salvage form of modified internal hemipelvectomy and wide margin resection. She opted for limb salvage. She underwent internal hemipelvectomy with wide margin resection of soft tissue and proximal femur along with postoperative albendazole therapy. She was able to walk again after a very long period. Currently she is 5-years postreconstructive surgery. She is infection free and ambulant without support. CONCLUSIONS: Hydatid bone disease is a rare entity in our part of the world but a careful history and thorough look at the initial images of our patient would have led to the suspicion of pathologic fracture and subsequent early diagnosis of this difficult problem. A second important learning point in this case was the lack of early referral to a center where this difficult problem could have been handled effectively. This could have minimized the physical, mental and financial stress to the patient and her family.

Terrorist attacks in the largest metropolitan city of Pakistan: Profile of soft tissue and skeletal injuries from a single trauma center.

BACKGROUND: Pakistan has been hugely struck with massive bomb explosions (car and suicide bombs) resulting in multiple casualties in the past few years. The aim of this study is to present the patterns of skeletal and soft tissue injuries and to review the outcome of the victims who presented to our hospital. METHODS: This is a retrospective chart review from January 2008 to December 2012. The medical record numbers of patients were obtained from the hospital Health Information and Management Sciences (HIMS) as per the ICD-9 coding. RESULTS: During the study period, more than 100 suicide and implanted bomb blast attacks took place in the public proceedings, government offices, residential areas and other places of the city. Altogether 262 patients were enrolled in the study. The mean age of the patients was 31±14 years. The shrapnel inflicted wounds were present on to the upper limb in 24 patients and the lower limb in 50. CONCLUSION: Long bone fractures were the most common skeletal injuries. The fractures were complicated by penetrating fragments and nails which result in post operative infections and prolonged hospital stay.

Salvage of infected non-union of the tibia with an Ilizarov ring fixator.

PURPOSE: To review outcomes of 24 patients who underwent Ilizarov ring fixation for infected nonunion of the tibia. METHODS: Medical records of 21 men and 3 women aged 13 to 74 (mean, 38) years who underwent Ilizarov ring fixation for infected non-union of the tibia were reviewed. The mean bone defect was 3.3 (range, 2-5) cm. The mean time from injury to presentation was 11.9 (range, 1-36) months. The mean number of previous surgeries was 2 (range, 0-14). A local flap was used in 2 patients and a free flap was used in one patient. Nine of the patients underwent Ilizarov ring fixation without soft tissue and bony resection, as inadequate stability was the reason for non-union. Patients were assessed using the Association for the Study and Application of the Method of Ilizarov criteria. RESULTS: Patients were followed up for a mean of 11 (range, 8-46) months. Functional outcome was excellent in 8 patients, good in 12, fair in 2, and failure in one, whereas bone union outcome was excellent in 6 patients, good in 14, fair in one, and poor in 2. The mean time to union was 8 (range, 3-31) months. The mean external fixation index was 4.2 (range, 1.5-15.7) cm/month. Complications encountered were pin tract infection (n=5), re-fracture (n=2), soft tissue impingement by Ilizarov rings (n=2), recurrence of wound infection (n=1), mal-union (n=1), and mortality (n=1). CONCLUSION: Ilizarov ring fixation is a viable option for infected non-union of the tibia. Adequate assessment of bone union is crucial before removal of fixator to prevent re-fracture.