71 research outputs found
Structure, Dynamics and Surface Hydrophobicity of the Cataract-Associated Mutant, Pro23Thr of Human Gamma D-crystallin: Molecular Basis of Cataract Formation
Prevention Mechanism on DDOS Attacks by using Multilevel Filtering of Distributed Firewalls
In the past decade, it has been found that DDoS has proved to be the most dangerous attack. IP spoofing is one of the kinds of DDoS attack which is emerging as a big threat in today’s world of technology. The Proposed Framework is a unique technique composed of distributed firewalls and hop count based filtering, it can be used to prevent such kind of DDoS attack. At The primary level, distributed firewalls filters the IP addresses which can be either Internet or Intranet. Along with this it also provide various other advantages such as reducing the dependency of network topology. At secondary level, hop count and TTL based filtering provides more secure level of filtration. In this paper, we have proposed a new framework which reduces the limitations of previous conventional techniques.
DOI: 10.17762/ijritcc2321-8169.15032
Gradual distraction for treatment of severe knee flexion contractures using the Ilizarov’s apparatus
Background: Knee flexion contractures result in a significant amount of functional disability due to reduced mobility and limb length discrepancy. Treatment options include non-surgical methods like serial casting, dynamic splinting and traction or surgical methods like osteotomies and soft tissue procedures. External fixation has emerged as a highly successful means of achieving controlled gradual correction of joint contractures with low rates of complications including recurrence. The aim of this study is to evaluate the functional outcome in terms of residual deformity and change in ambulatory status following correction using the Ilizarov’s apparatus.Methods: 12 patients with knee flexion contractures ranging from 20°-70° underwent correction using the Ilizarov’s external fixator (IEF). The use of simple mathematic formulae enabled us to calculate and estimate the rate and duration of distraction. End results were assessed at one year by the residual contracture as: Excellent: 0-5°, Good: 6-15°, Fair: 16-30° and Poor: >30°.Results: The functional assessment was graded as excellent in 7, good in 4 and fair in 1 out of 12 patients. All patients were independent ambulators and only 1 out of 12 patients required an additional orthosis for maintenance of the correction.Conclusions: The IEF is a safe and precise modality even for the most complex contractures of the knee. Accurate placement of the hinges along the center of rotation of the knee avoids undue subluxation of the tibia during correction. In order to ensure a low rate of complications, it is imperative to have a detailed pre-operative plan and all principles of fixation should be meticulously adhered to.
Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy
Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.</p
Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy
Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.</p
Thermodynamic Studies on the Cataract-Associated Mutant, E107a, of Human Gamma-D Crystallin: Molecular Basis for Cataract Formation
Reduced efficacy of insulin detemir in controlling hyperglycemia during pregnancy: An interesting case report
Nuclear Magnetic Resonance Structure of a Major Lens Protein, Human gamma C-Crystallin: Role of the Dipole Moment in Protein Solubility
A hallmark of the crystallin proteins is their exceptionally high solubility, which is vital for maintaining the high refractive index of the eye lens. Human gamma C-crystallin is a major gamma-crystallin whose mutant forms are associated with congenital cataracts but whose three-dimensional structure is not known. An earlier study of a homology model concluded that human gamma C-crystallin has low intrinsic solubility, mainly because of the atypical magnitude and fluctuations of its dipole moment. On the contrary, the high-resolution tertiary structure of human gamma C-crystallin determined here shows unequivocally that it is a highly soluble, monomeric molecule in solution. Notable differences between the orientations and interactions of several side chains are observed upon comparison to those in the model. No evidence of the pivotal role ascribed to the effect of dipole moment on protein solubility was found. The nuclear magnetic resonance structure should facilitate a comprehensive understanding of the deleterious effects of cataract-associated mutations in human gamma C-crystallin
Deamidation of Human γS-Crystallin Increases Attractive Protein Interactions: Implications for Cataract
Deamidation
of proteins is one of the most prevalent post-translational
modifications found upon aging, and in age-onset diseases. Specific
asparagine and glutamine residues are often selectively deamidated
during this process. In the human lens, deamidation has been shown
to occur in many crystallins, but it is not clear how these deamidated
proteins lead to lens opacity or cataract. Here we have modeled <i>in vitro</i> the effect of deamidation of specific asparagine
and glutamine residues in human recombinant γS-crystallin (HGS)
on the solution properties of the protein. The residues selected for
deamidation <i>in vitro</i> are those that are found to
be deamidated in aged and cataractous lenses <i>in vivo</i>. Two derivatives were prepared, one with Asn76 and Asn143 deamidated
(2N-HGS) and the other with two additional Gln residues (92 and 120)
deamidated (2N2Q-HGS). Isoelectric focusing measurements showed the
expected lowering of the pI from 6.9 in HGS to ∼6.5 in 2N-HGS
and to ∼6.1 in 2N2Q-HGS. However, spectroscopic studies showed
no significant change in the secondary and tertiary structures of
the deamidated proteins relative to the wild type. The stability of
2N-HGS and 2N2Q-HGS, as measured by guanidinium hydrochloride unfolding,
also remained comparable to that of HGS. The main difference was the
altered protein–protein interaction among the three proteins.
The net repulsive interactions that are characteristic of HGS are
diminished in the deamidated derivatives as evidenced by static light
scattering measurements of the second virial coefficient, <i>B</i><sub>2</sub> (<i>B</i><sub>2</sub> values for
HGS, 2N-HGS, and 2N2Q-HGS of 8.90 × 10<sup>–4</sup>, 7.10
× 10<sup>–4</sup>, and 6.65 × 10<sup>–4</sup> mL mol g<sup>–2</sup>, respectively). Further substantiation
is provided by estimates of the excess binding energy of protein–protein
interactions in the condensed phase, obtained from measurements of
the PEG-induced liquid–liquid phase separation profiles for
the three proteins. The data suggest that enhanced attractive protein–protein
interactions, arising from the deamidation of HGS, promote protein
aggregation, thereby leading to increased light scattering and opacity
over time
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