Chaos and bifurcations of a two-dimensional hepatitis C virus model with hepatocyte homeostasis.

In this paper, we delve into the intricate local dynamics at equilibria within a two-dimensional model of hepatitis C virus (HCV) alongside hepatocyte homeostasis. The study investigates the existence of bifurcation sets and conducts a comprehensive bifurcation analysis to elucidate the system's behavior under varying conditions. A significant focus lies on understanding how changes in parameters can lead to bifurcations, which are pivotal points where the qualitative behavior of the system undergoes fundamental transformations. Moreover, the paper introduces and employs hybrid control feedback and Ott-Grebogi-Yorke strategies as tools to manage and mitigate chaos inherent within the HCV model. This chaos arises due to the presence of flip and Neimark-Sacker bifurcations, which can induce erratic behavior in the system. Through the implementation of these control strategies, the study aims to stabilize the system and restore it to a more manageable and predictable state. Furthermore, to validate the theoretical findings and the efficacy of the proposed control strategies, extensive numerical simulations are conducted. These simulations serve as a means of confirming the theoretical predictions and provide insight into the practical implications of the proposed control methodologies. By combining theoretical analysis with computational simulations, the paper offers a comprehensive understanding of the dynamics of the HCV model and provides valuable insights into potential strategies for controlling and managing chaos in such complex biological systems.

Bifurcations and chaos control in a discrete Rosenzweig-Macarthur prey-predator model.

In this paper, we explore the local dynamics, chaos, and bifurcations of a discrete Rosenzweig-Macarthur prey-predator model. More specifically, we explore local dynamical characteristics at equilibrium solutions of the discrete model. The existence of bifurcations at equilibrium solutions is also studied, and that at semitrivial and trivial equilibrium solutions, the model does not undergo flip bifurcation, but at positive equilibrium solutions, it undergoes flip and Neimark-Sacker bifurcations when parameters go through certain curves. Fold bifurcation does not exist at positive equilibrium, and we have studied these bifurcations by the center manifold theorem and bifurcation theory. We also studied chaos by the feedback control method. The theoretical results are confirmed numerically.

Discrete-time COVID-19 epidemic model with chaos, stability and bifurcation.

In this paper, we explore local behavior at fixed points, chaos and bifurcations of a discrete COVID-19 epidemic model in the interior of R + 5 . It is explored that for all involved parametric values, COVID-19 model has boundary fixed point and also it has an interior fixed point under certain parametric condition(s). We have investigated local behavior at boundary and interior fixed points of COVID-19 model by linear stability theory. It is also explored the existence of possible bifurcations at respective fixed points, and proved that at boundary fixed point there exists no flip bifurcation but at interior fixed point it undergoes both flip and hopf bifurcations, and we have explored said bifurcations by explicit criterion. Moreover, chaos in COVID-19 model is also investigated by feedback control strategy. Finally, theoretical results are verified numerically.

Discrete-time COVID-19 epidemic model with bifurcation and control.

The local dynamics with different topological classifications, bifurcation analysis and chaos control in a discrete-time COVID-19 epidemic model are investigated in the interior of $ \mathbb{R}_+^3 $. It is proved that discrete-time COVID-19 epidemic model has boundary equilibrium solution for all involved parameters, but it has an interior equilibrium solution under definite parametric condition. Then by linear stability theory, local dynamics with different topological classifications are investigated about boundary and interior equilibrium solutions of the discrete-time COVID-19 epidemic model. Further for the discrete-time COVID-19 epidemic model, existence of periodic points and convergence rate are also investigated. It is also investigated the existence of possible bifurcations about boundary and interior equilibrium solutions, and proved that there exists no flip bifurcation about boundary equilibrium solution. Moreover, it is proved that about interior equilibrium solution there exists hopf and flip bifurcations, and we have studied these bifurcations by utilizing explicit criterion. Next by feedback control strategy, chaos in the discrete COVID-19 epidemic model is also explored. Finally numerically verified theoretical results.

Discrete-time predator-prey model with flip bifurcation and chaos control.

We explore the local dynamics, flip bifurcation, chaos control and existence of periodic point of the predator-prey model with Allee effect on the prey population in the interior of $\mathbb{R}^*{_+^2}$. Nu-merical simulations not only exhibit our results with the theoretical analysis but also show the complex dynamical behaviors, such as the period-2, 8, 11, 17, 20 and 22 orbits. Further, maximum Lyapunov exponents as well as fractal dimensions are also computed numerically to show the presence of chaotic behavior in the model under consideration.

A cell culture model for investigation of synapse influenceability: epigenetics, expression and function of gene targets important for synapse formation and preservation in SH-SY5Y neuroblastoma cells differentiated by retinoic acid.

SH-SY5Y neuroblastoma cells are frequently used for different neuronal cell culture models. As there is no "gold-standard", miscellaneous protocols exist to differentiate these cells into a neuronal cell type. Here, the aim was to find a differentiation condition making cells suitable for investigation of influenceability of synapses by environmental conditions in pharmacologic experiments. For this purpose, effects on synapse molecules should be somehow rateable and cells should be usable for functional analysis like calcium imaging. A system like this is desirable for example in basic research concerning schizophrenia, depression, autism or neurodegeneration as synaptic plasticity and neuronal maturation are known to have a significant impact in these diseases. Cells grown on laminin-coated glass cover slips and treated with 50 µM retinoic acid (RA) turned out to show most convincing morphological signs of neuronal differentiation and attached strongly to the ground, thereby also fulfilling preconditions for functional analysis. Systematic characterisation of this differentiation condition in comparison to non-treated controls revealed lower methylation rates and higher expression of most candidate molecules relevant for formation, preservation and function of synapses as well as differential function. In conclusion, this combination of differentiation strategy and markers seems to be a suitable system to estimate synapse modifications in basic research as it could help to identify possible dedifferentiating effects. To our knowledge, differentiation of SH-SY5Y has not been described as systematic before regarding comprehensiveness of the set of investigated synapse molecules and coverage of applied methods spanning from epigenetics to protein function. Furthermore, this is the first time that SH-SY5Y cells were differentiated on glass cover slips to an extent making them suitable for investigation of synapse molecules as part of stable intercellular connections in downstream functional analyses.

Restarting Thalidomide-Dexamethasone Regimen in a Post-Abortive Female with Multiple Myeloma: Effective Clinical Response Possible.

Nowadays, the prevalence of Multiple Myeloma (MM) seems to have been increasing among young females. Here, we report that thalidomide is contraindicated in pregnant women diagnosed with MM and those desirous of subsequent pregnancy. In this case report, we compared the clinical response of Thalidomide-Dexamethasone therapy in a post-abortive woman with persistently elevated ß-hCG levels due to retained products of conception, undergoing hysterectomy later. This case report underlines the clinical significance of age, the effect of Thalidomide-Dexamethasone therapy even after initial discontinuation and the response to high ß-hCG levels.

Neimark-Sacker bifurcation of a two-dimensional discrete-time predator-prey model.

In this paper, we study the dynamics and bifurcation of a two-dimensional discrete-time predator-prey model in the closed first quadrant [Formula: see text]. The existence and local stability of the unique positive equilibrium of the model are analyzed algebraically. It is shown that the model can undergo a Neimark-Sacker bifurcation in a small neighborhood of the unique positive equilibrium and an invariant circle will appear. Some numerical simulations are presented to illustrate our theocratical results and numerically it is shown that the unique positive equilibrium of the system is globally asymptotically stable.

Mitigation of 5-fluorouracil-induced liver damage in rats by vitamin C via targeting redox-sensitive transcription factors.

Adverse complications associated with antineoplastic drug-based cancer therapy are the major clinical drawbacks. Oxidative stress and inflammation play a major role in the damage due to cancer therapy. In the current study, we investigated the modulatory effect of vitamin C (Vit. C) on liver toxicity induced by 5-fluorouracil (5-FU) in rats. Animals were divided into four groups. Animals in group I received vehicle. Oral gavage of Vit. C (500 mg kg-1 body weight (b.wt.)) was given to the animals in group III and group IV. 5-FU (150 mg kg-1 b.wt.) was injected intraperitoneally to the animals in group II and group III. Findings of the present study revealed that oral administration of Vit. C significantly ameliorated the level of lipid peroxidation and the activity of myeloperoxidase. Vit. C administration markedly reduced the activation of nuclear factor κB and expression of cyclooxygenase 2, whereas nuclear translocation of nuclear factor erythroid 2-related factor 2 was increased. Hepatic histopathological analyses further supported the protective effect of Vit. C. Findings of the current study demonstrate that the toxic free radicals and inflammatory mediators generated due to chemotherapy play a critical role in 5-FU-induced hepatic damage. Attenuating action of Vit. C may be due to the modulation of redox-sensitive transcription factors and associated target molecules.

Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study.

5-Fluorouracil is one of the most commonly used anticancer drugs for the treatment of various types of cancer but has potential adverse effects such as intestinal mucositis, renal, hepatic, and reproductive organ toxicity. Attention has been given to approaches to reduce the side effects and improve the therapeutic effectiveness of chemotherapeutic drugs. In this study, we have investigated the protective effect of taurine (Tau) on 5-fluorouracil (5-FU) induced adverse effects in Wistar rats. Animals were divided into four groups with six animals (n = 6) in each group. Group I received vehicle only and served as control group. Groups II, III, and IV animals were given oral gavage of 5-FU at 50 mg/kg body weight for 4 days. Tau was given to the animals of groups III and IV 30 min prior to 5-FU administration. We observed marked elevation in the myeloperoxidase (MPO) activity after 5-FU administration, which was reversed by Tau pretreatment. Histological observation of liver, kidney, intestine, testis, and prostate revealed that 5-FU administration resulted in anomalies like distortion of normal cellular architecture, infiltration of inflammatory cells, and loss of cellular integrity. These histopathological changes were markedly suppressed by Tau treatment. In conclusion, biochemical and histological findings of this study suggest that Tau has strong preventive potential against complications of anticancer drug 5-FU and hence Tau may play an important role in combinational chemotherapy to enhance the therapeutic efficacy of anticancer drugs.

Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium: Interception by naringenin.

Industrial solvents pose a significant threat to the humankind. The mechanisms of their toxicity still remain in debate. Trichloroethylene (TCE) is a widespread industrial solvent responsible for severe liver dysfunction, cutaneous toxicity in occupationally exposed humans. We utilized an in vitro system of human epidermal keratinocyte (HaCaT) cells in this study to avoid complex cell and extracellular interactions. We report the cytotoxicity of organic solvent TCE in HaCaT and its reversal by a natural flavanone, naringenin (Nar). The cytotoxicity was attributed to the rapid intracellular free calcium (Ca(2+)) release, which might lead to the elevation of protein kinase C along with robust free radical generation, instability due to energy depletion, and sensitization of intracellular stress signal transducer nuclear factor κB. These effects were actually seen to induce significant amount of genomic DNA fragmentation. Furthermore, all these effects of TCE were effectively reversed by the treatment of Nar, a natural flavanone. Our studies identify intracellular Ca as a unique target used by organic solvents in the cytotoxicity and highlight the Ca(2+) ion stabilizer properties of Nar.

Neglected orthopedic oncology--Causes, epidemiology and challenges for management in developing countries.

BACKGROUND: Management of malignant bone and soft tissue tumors remains an overwhelming confront to orthopedic surgeons. The challenge is discriminating in developing countries due to inadequate diagnostic and therapeutic amenities and unawareness. A lot has been discussed about the neglected orthopedic trauma, but the published literature on the causes and management of neglected bone and soft tissue tumors is sparse. Hence, current study was undertaken to highlight the causes of neglect and therapeutic challenges for managing these neglected tumors in developing countries. AIMS AND OBJECTIVES: To determine the causes of neglect of malignant bone and soft tissue tumors, their epidemiology (including their relative frequencies, age, gender discrimination, anatomical sites of occurrence and histological characteristics) and difficult aspect of management due to neglect or delayed presentation. MATERIALS AND METHODS: This was an appraisal of the neglected malignant bone and soft tissue tumors presented to J. N. Medical College and Hospital from June 2008 to May 2013. Criteria for labeling the tumor as neglected malignant bone and soft tissue tumor was delayed presentation (>3 months), locally advanced disease, ulceration, sepsis, fungating mass or metastasis at the time of presentation. All the cases were reviewed and analyzed for age, gender, histological types, educational status and socioeconomic status of the family, any prior treatment by traditional bone setters or registered medical practitioner, cause of delay for seeking medical advice. We have also analyzed the treatment given at our institute and the outcome of the tumor. OBSERVATIONS AND RESULTS: Eighteen patients fulfilled the criteria for neglected malignant bone and soft tissue tumors, hence were included in study. Eight cases were of osteosarcoma, five cases were of Ewing's sarcoma, three cases were of chondrosarcoma and 1 case each was of pleomorphic liposarcoma and primary lymphoma of bone. According to Enneking staging system 11 cases were of stage III (distant metastasis) and 7 were stage II-B. Seven were females, and 11 were males. Age range was 5-68 years. 15 patients (83.3%) belonged to low socioeconomic status with 17 patients (94.4%) belonged to uneducated background. Cause of delay in seeking medical advice was neglect by the patient and family due to financial constraints, cultural and religious believes, lack of access to health care facilities, consultation with traditional bone setters and even misdiagnosis by qualified orthopedic surgeons. The tumors included were all unresectable and of huge sizes, hence were managed with amputation/dis-articulation, chemotherapy or radiation. CONCLUSION: The current study tries to highlight the causes and quantity of neglect of malignant bone and soft tissue tumors prevalent in our country, which poses a therapeutic challenge for management and consequent mutilating surgeries with poor outcome resulting in loss of extremity and existence.

18-ß Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: Role in hyperproliferation, inflammation and oxidative stress.

2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-ß Glycyrrhetinic acid (18ß-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18ß-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18ß-GA at two different doses (45 and 75 mg kg(-1) b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18ß-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18ß-GA. Our findings suggest that pretreatment with 18ß-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation.

Chemopreventive effects of aloin against 1,2-dimethylhydrazine-induced preneoplastic lesions in the colon of Wistar rats.

Chemoprevention opens new window in the prevention of all types of cancers including colon cancer. Aloin, an anthracycline in plant pigment, can be utilized as a protective agent in cancer induction. In the present study, we have evaluated the chemopreventive efficacy of aloin against 1,2-dimethylhydrazine (DMH)-induced preneoplastic lesions in the colon of Wistar rats. DMH-induced aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have been used as biomarkers of colon cancer. Efficacy of aloin against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, ACF, MDF, histopathological changes, and expression levels of molecular markers of inflammation and tumor promotion. Aloin pretreatment ameliorates the damaging effects induced by DMH through a protective mechanism that involved reduction in increased oxidative stress enzymes (p < 0.001), ACF, MDF, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6, proliferating cell nuclear antigen protein expression, and tumor necrosis factor-α (p < 0.001) release. From the results, it could be concluded that aloin clearly protects against chemically induced colon toxicity and acts reasonably by inducing antioxidant level, anti-inflammatory and antiproliferative markers.

Perillyl alcohol as a protective modulator against rat hepatocarcinogenesis via amelioration of oxidative damage and cell proliferation.

In the present study, we have evaluated the chemopreventive effects of perillyl alcohol (POH) against diethylnitrosamine-initiated and 2-AAF (2-acetylaminofluorine)-promoted hepatocarcinogenesis in Wistar rats. Efficacy of POH against 2-AAF-induced hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, histopathological changes and expression levels of proliferative markers. 2-AAF is a potent hepatotoxicant and a hepatic carcinogen that induces its effect by causing oxidative stress. Pre-treatment of POH prevented oxidative stress and tumour incidences. POH suppressed 2-AAF-induced early tumour markers, namely ornithine decarboxylase activity, thymidine phosphorylase and proliferating cell nuclear antigen (PCNA) protein and also suppressed the expression of pro-apoptotic protein P53. Histopathological findings revealed that POH-pretreated groups showed marked recovery. From our results, it could be concluded that POH markedly protects against chemically induced liver cancer and acts possibly by virtue of its antioxidant and antiproliferative activities.

Fixation using cannulated screws and fibular strut grafts for fresh femoral neck fractures with posterior comminution.

PURPOSE: To evaluate the use of fibular grafting for fresh femoral neck fractures with posterior comminution. METHODS: 18 women and 15 men aged 20 to 60 years underwent osteosynthesis and fibular strut grafting supplemented with 7.0-mm cannulated hip screws for Garden grades III (n=21) and IV (n=12) femoral neck fractures associated with posterior comminution. All fractures were reduced by closed methods, and no hip was aspirated. Clinical and radiological outcomes were evaluated. RESULTS: The mean delay in presentation after injury was 3.2 (range, 1-12) days. The mean delay in operation was 8.8 (range, 5-21) days. The mean follow-up period was 2 (range, 1-4) years. According to the Harris hip score, outcome was good to excellent in 20 patients, fair in 7, and poor in 6. 27 of the 33 patients achieved bone union after a mean of 4.7 (range, 4.2-7) months. In 5 patients, the bone was united with a mean of 10º of varus collapse and a mean of 1 cm of shortening. Six patients had non-union. Other complications included screw migration in the joint space (n=1), graft migration into the joint space (n=3), and screw pullout (n=5). No patient had avascular necrosis of the femoral head. CONCLUSION: Osteosynthesis and fibular grafting for freshly displaced femoral neck fractures with posterior comminution is an inexpensive and technically less demanding procedure for retaining a stable, painless, mobile, and functional hip.

Primary hydatid cyst of pancreas with acute pancreatitis.

CONTEXT: Primary hydatid disease of the pancreas is very rare and even rarer to cause pancreatitis. CASE REPORT: We report the case of a 20-year-old man who presented with abdominal pain and an epigastric mass. A diagnosis of a pancreatic hydatid cyst was established by ultrasonography and CT scan before surgery. The treatment consisted of laparoscopic cyst evacuation with omentoplasty. The recovery was uneventful and the patient has remained symptom free so far. CONCLUSIONS: Hydatid disease should be considered in the differential diagnosis of all cystic masses in the pancreas, especially in the geographical regions where the disease is endemic.

Neoadjuvant chemo-radiotherapy and rectal cancer: can the UK watch and wait with Brazil?

OBJECTIVE: It has recently been reported that up to one-third of patients with nonmetastatic distal rectal cancer managed with neoadjuvant chemoradiation therapy (CRT) had a complete clinical response (cCR) to treatment. In the selected cases, this has been used as the sole treatment. The aim of this study was to determine the frequency of complete pathological response for patients receiving CRT in one centre in the UK. METHOD: Patients receiving 6 weeks of neoadjuvant CRT were identified using the two cancer audit databases in two different tertiary hospitals from January 2002 to November 2007. Pathology was reviewed and the histopathological response of the resected specimen to CRT was evaluated using the Mandard classification (1 = complete response, 5 = no response) RESULTS: One hundred and thirty-two consecutive patients [median age 61 (range 44-86) years, 90 men] with nonmetastatic locally advanced rectal cancer received neoadjuvant chemo radiotherapy between 2002 and 2007 followed by resection of the tumour. Data were available from 129 patients. CONCLUSION: Only 13 out of 132 (10%) of patients had a complete pathological response. This is one-third of the cCR previously reported. Nonsurgical therapy for rectal cancer using the Habr-Gama treatment algorithm may only be effective in a very small proportion of patients with rectal cancer in the UK and nonoperative treatment would not be recommended.

Ethnic differences and determinants of diabetes and central obesity among South Asians of Pakistan.

AIMS: To study the within ethnic subgroup variations in diabetes and central obesity among South Asians. METHODS: Data from 9442 individuals age > or = 15 years from the National Health Survey of Pakistan (NHSP) (1990-1994) were analysed. Diabetes was defined as non-fasting blood glucose > or = 7.8 mmol/l, or known history of diabetes. Central obesity was measured at the waist circumference. Distinct ethnic subgroups Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi were defined by mother tongue. RESULTS: The age-standardized prevalence of diabetes varied among ethnic subgroups (P = 0.002), being highest among the Muhajirs (men 5.7%, women 7.9%), then Punjabis (men 4.6%, women 7.2%), Sindhis (men 5.1%, women 4.8%), Pashtuns (men 3.0%, women 3.8%), and lowest among the Baluchis (men 2.9%, women 2.6%). While diabetes was more prevalent in urban vs. rural dwellers [odds ratio (OR) 1.50, 95% confidence interval (CI) 1.24, 1.82], this difference was no longer significant after adjusting for central obesity (OR 1.15, 95% CI 0.95, 1.42). However, the ethnic differences persisted after adjusting for major sociodemographic risk factors (unadjusted OR for Pashtun vs. Punjabi 0.59, 95% CI 0.42, 0.84, adjusted OR 0.54, 95% CI 0.37, 0.78). Ethnic variation was also observed in central obesity, which varied with gender, and did not necessarily track with ethnic differences in diabetes. CONCLUSIONS: Unmeasured environmental or genetic factors account for ethnic variations in diabetes and central obesity, and deserve further study.

Distinct types of T-cell help for the induction of a humoral immune response to Streptococcus pneumoniae.

Studies have indicated that purified soluble polysaccharide antigens can elicit T cell-independent Ig responses in vivo, although these responses can be modulated by T cells in a noncognate manner. Relatively little is known, however, concerning the parameters that regulate polysaccharide-specific, as well as protein-specific, Ig isotype responses to an intact extracellular bacterium. Using the murine in vivo humoral response to intact Streptococcus pneumoniae as a model it can be shown that CD4+ T-cell receptor alphabeta+ T cells deliver help for both polysaccharide- and protein-specific Ig responses. However, these responses differ fundamentally in their mechanism of action.