Surgical patterns in osteoporotic vertebral compression fractures

Purpose

To report morphological patterns of osteoporotic vertebral compression fractures (OVCFs) presenting for surgery. To describe surgical options based on fracture pattern. To evaluate clinical and radiological outcome.

Methods

Forty consecutively operated OVCFs nonunion patients were retrospectively studied. We define four patterns of OVCFs that needed surgical intervention. Group 1 mini open vertebroplasty (N = 10) no neurologic deficits and kyphotic deformity, but with intravertebral instability and significant radiological spinal canal compromise. Group 2 with neurologic deficits (N = 24) (2A)—transpedicular decompression (TPD) with instrumentation (N = 14). Fracture morphology similar to (1) and localized kyphosis <30° (2B)—pedicle subtraction osteotomy (PSO) with instrumentation (N = 10). Fracture morphology similar to (1) and local kyphosis >30°. Group 3 posterolateral decompression with interbody reconstruction (N = 06) endplate(s) destroyed, with instability at discovertebral junction, with neurologic deficit. Average follow-up was 34 months. VAS, ODI and Cobb angle were recorded at 3, 6, 12 months and yearly.

Results

There was significant improvement in the clinical (VAS and ODI) scores and radiologic outcome in each group at last follow-up. 30 patients out of 40, had neurologic deficits (Frankel’s grade C = 16, Frankel’s grade D = 14). The motor power gradually improved to Frankel’s grade E. Average duration of surgery was 97 min. Average blood loss was 610 ml.

Conclusion

Different surgical techniques were used to suit different fracture patterns, with good clinical and radiological results. This could be a step forward in devising an algorithm to surgical treatment of OVCF nonunions.     

Statistical mechanics of convergent evolution in spatial patterning

We explore how the genotype–phenotype map determines convergent evolution in a simple model of spatial gene regulation during development. Evolution is simulated via a Monte Carlo scheme that incorporates mutation, selection, and genetic drift, by using a bottom-up model of gene regulation with a fitness function that is optimized by a switch-like response to a morphogen gradient. We find that even for very simple regulation, the genotype–phenotype map gives rise to an emergent fitness landscape of remarkable complexity. This leads to a richness of evolutionary behavior as population size is increased that parallels the thermodynamics of physical systems as temperature decreases. Convergence is controlled by the existence of sufficiently dominant global optima in “free fitness,” which is a quantity that is the balance of mutational entropy and fitness. In independent simulations at low population sizes, we find convergence to a phenotype of suboptimal fitness due to the multiplicity or entropy of solutions. This contrasts with convergence to the optimal fitness phenotype at high population size. However, at sufficiently large population sizes, we find convergence in only the phenotypes with greatest effect on fitness, whereas noncritical phenotypes exhibit divergence due to quenched disorder on a locally rough landscape. Our results predict that for large populations, the evolution of even simple gene regulatory circuits may be glassy-like, such that, counter to the commonly accepted view that conservation implies function, many conserved phenotypes are simply frozen accidents of little consequence to the fitness of the organism.     

Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation

Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241–290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3–30 μg/mL for TOL and 1–10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit.     

Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells

There is an unmet need to develop new, more effective and safe therapies for the aggressive forms of triple negative breast cancers (TNBCs). While up to 20% of women under 50 years of age with TNBC harbor germline mutations in BRCA1, and these tumors are sensitive to treatment with poly(ADP) ribose polymerase inhibitors, a majority of TNBCs lack BRCA1 mutations or loss of expression. Findings presented here demonstrate that by attenuating the levels of DNA damage response and homologous recombination proteins, pan-histone deacetylase inhibitor (HDI) treatment induces ‘BRCAness’ and sensitizes TNBC cells lacking BRCA1 to lethal effects of PARP inhibitor or cisplatin. Treatment with HDI also induced hyperacetylation of nuclear hsp90. Similar effects were observed following shRNA-mediated depletion of HDAC3, confirming its role as the deacetylase for nuclear HSP90. Furthermore, cotreatment with HDI and ABT-888 induced significantly more DNA strand breaks than either agent alone, and synergistically induced apoptosis of TNBC cells. Notably, co-treatment with HDI and ABT-888 significantly reduced in vivo tumor growth and markedly improved the survival of mice bearing TNBC cell xenografts. These findings support the rationale to interrogate the clinical activity of this novel combination against human TNBC, irrespective of its expression of mutant BRCA1.     

Total nasal reconstruction using composite radial forearm free flap and forehead flap as a one-stage procedure with minor revision

The refashioning of the many distinct structures necessary for successful anatomical and aesthetic reconstruction of the nose after total rhinectomy is difficult. Several significant operations are needed to produce good aesthetic results with functional patency of the nasal airway. We describe a method using autologous grafts that has produced good results on both occasions when it was done. It has the advantage of only one major operation and one subsequent minor revision.     

Low cytosine triphosphate synthase 2 expression renders resistance to 5-fluorouracil in colorectal cancer

Understanding the determinants of resistance of 5-fluorouracil (5FU) is of significant value to optimising administration of the drug, and introducing novel agents and treatment strategies. Here, the expression of 92 genes involved in 5FU transport, metabolism, co-factor (folate) metabolism and downstream effects was measured by real-time PCR low density arrays in 14 patient-derived colorectal cancer xenografts characterised for 5FU resistance. Candidate gene function was tested by siRNA and uridine modulation, and immunoblotting, apoptosis and cell cycle analysis. Predictive significance was tested by immunohistochemistry of tumours from 125 stage III colorectal cancer patients treated with and without 5FU. Of 8 genes significantly differentially expressed between 5FU sensitive and resistant xenograft tumours, CTPS2 was the gene with the highest probability of differential expression (p=0.008). Reduction of CTPS2 expression by siRNA increased the resistance of colorectal cancer cell lines DLD1 and LS174T to 5FU and its analogue, FUDR. CTPS2 siRNA significantly reduced cell S-phase accumulation and apoptosis following 5FU treatment. Exposure of cells to uridine, a precursor to the CTPS2 substrate uridine triphosphate, also increased 5FU resistance. Patients with low CTPS2 did not gain a survival benefit from 5FU treatment (p=0.072), while those with high expression did (p=0.003). Low CTPS2 expression may be a rationally-based determinant of 5FU resistance.     

Study on Obesity and Influence of Dietary Factors on the Weight Status of an Adult Population in Jamnagar City of Gujarat: A Cross-Sectional Analytical Study

Background:

Obesity has reached epidemic proportions globally and is a major contributor to the global burden of chronic diseases. Dietary factors are the major modifiable factors through which many of the external forces promoting weight gain act.

Objectives:

The objectives were to find the prevalence of overweight and obesity in the urban population of Jamnagar and to explore the effect of dietary factors on the weight status of the people.

Materials and Methods:

A cross-sectional study was conducted among the adult population of Jamnagar city. Cluster sampling technique was used to select study samples. Data were collected in a prestructured questionnaire by interviewing subjects through house-to-house visits. Data were analyzed in Epi Info and appropriate statistical methods were used.

Results:

The prevalence of overweight and obesity was found to be 22.04% and 5.20%, respectively. Overweight was more prevalent in females than males. The prevalence rose with an increase in age up to 60 years. Among dietary factors, the total calorie intake and habit of snacking had a positive association with weight gain (P < 0.05). The mean intake of oil was more and the mean intake of vegetables was less among overweight subjects than nonoverweight subjects (P < 0.05).

Conclusion:

The prevalence of overweight and obesity in the urban population in Jamnagar was found to be 22.04% and 5.20%, respectively. Total calorie intake as well as composition of diet was the important dietary factor affecting weight gain.