STUDY DESIGN: Prospective clinical study. PURPOSE: The purpose of this study was to evaluate the effect of interlaminar fusion and short segment pedicle screw fixation on thoracolumbar vertebral injuries for preventing pain and post-traumatic kyphosis. OVERVIEW OF LITERATURE: The treatment of thoracolumbar injuries continues to be one of the most controversial areas in spine care. The main aim of surgical treatment is to decompress the spinal cord or nerve roots, realign the spine, and correct or prevent post-traumatic kyphosis. We evaluated the outcome of interlaminar fusion along with posterior decompression and short segment pedicle screw fixation in patients with thoracolumbar fractures with neurological deficit. METHODS: Twenty-two patients with traumatic thoracolumbar vertebral injuries and neurological deficit underwent short segment pedicle screw fixation above and below the fractured vertebrae, posterior decompression, and interlaminar fusion using a bone graft. RESULTS: All patients were followed up for 12 months postoperatively. The average operative time and blood loss was 142 minutes and 214 mL, respectively. Of the 22 patients, 14 recovered completely. Of the nine patients with American Spinal Injury Association (ASIA) grade A disease, two improved by 1 grade, whereas one each improved by grades 2, 3, and 4, and four did not recover. Radiologically, vertebral kyphosis angle improved from 20.91 preoperatively to 15.73 postoperatively, sagittal index improved from 24.77 to 18.73, the sagittal plane kyphosis angle improved from 17.45 to 11.41, regional angle kyphosis improved from 14.73 to 10.14, the superior inferior end plate angle from 16.14 to 13.00, and mean anterior body compression improved from 36.26 to 27.64 postoperatively. No implant failed and no patient had neurological deterioration. CONCLUSIONS: Short segment pedicle screw fixation with posterior decompression and interlaminar fusion provided considerable reduction in kyphosis, restored the vertebral height of patients with thoracolumbar vertebral injuries and neurological deficit, and prevented development of delayed kyphotic deformity.
Clinical Study ; Congenital Abnormalities ; Decompression* ; Humans ; Kyphosis ; Neurologic Manifestations ; Operative Time ; Pedicle Screws* ; Prospective Studies ; Spinal Cord ; Spinal Injuries ; Spine ; Transplants

Bilateral distal anterior cerebral artery (DACA) aneurysms also called “kissing aneurysms” or “mirror aneurysm” are extremely rare, accounting for only 0.2% of all intracranial aneurysms. There have only been a few examples of mirror DACA aneurysms reported in the literature. Here, we report a rare case of mirror DACA aneurysm in a middle aged female with its successful clipping. Patient was admitted with severe headache and altered sensorium. Computed tomography (CT) head was suggestive of anterior inter-hemispheric hematoma. Digital subtraction angiography (DSA) was done which was suggestive of two distal anterior cerebral artery aneurysms located at same anatomical position. It was treated through microsurgical clipping. Mirror image DACA aneurysms are rare occurrence. All patients with ruptured DACA aneurysms should have angiography with 3D reconstruction studies. This aids in determining the aneurysm’s morphology and planning treatment accordingly.

Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma.
Breast Neoplasms* ; Breast* ; DNA Repair ; DNA* ; Drug Therapy ; Genotype ; Homologous Recombination ; Phenotype ; Radiotherapy

Among the genotoxic drug regimens, doxorubicin (DOX) is known for its high-dose side effects in several carcinomas, including cervical cancer. This study reports on testing the combined use of a DOX genotoxic drug and SCR-7 non-homologous end joining (NHEJ) inhibitor for HeLa cells. An in vitro DNA damaging assay of DOX was performed on plasmid and genomic DNA substrate. In vitro cytotoxicity was investigated using trypan blue dye exclusion, DNA metabolizing, and propidium iodide-based flow cytometric assays. DOX (between 20–100 μM) displayed clear DNA binding and interaction, such as the shearing and smearing of plasmid and genomic DNA. DNA metabolizing assay data indicate that HeLa lysate with DOX and SCR-7 treatment exhibited better in vitro plasmid DNA stability compared with DOX treatment alone. SCR-7 augmented the effects of low-dose DOX by demonstrating enhanced cell death from 15% to 50%. The flow cytometric data also supported that the combination of SCR-7 with DOX lead to a 23% increase in propidium iodide-based HeLa staining, thus indicating enhanced death. In summary, the inhibition of NHEJ DNA repair pathway can potentiate low-dose DOX to produce appreciable cytotoxicity in HeLa cells.
Cell Death ; DNA ; DNA Damage ; DNA End-Joining Repair ; DNA Repair ; Doxorubicin* ; Drug Therapy ; Genomic Instability ; HeLa Cells* ; Humans ; In Vitro Techniques ; Plasmids ; Propidium ; Trypan Blue ; Uterine Cervical Neoplasms

Complex craniovertebral junction (CVJ) defects account for a considerable proportion of CVJ diseases. Given the heavily assimilated C1, an unfavorable C1–C2 joint orientation, an overriding C2 superior facet, a low-hanging occiput, and an abnormal vertebral artery course with a high-riding vertebral artery, placement of C1 lateral mass screws might be difficult. To address this, a novel technique for placing C1 lateral mass screws that avoid vertebral artery injury, low-hanging occiput, and overriding C2 superior facet was developed in this study. This approach enables firm fixation of C1–C2 even in difficult situations where the placement of the C1 lateral mass is challenging.

Several genetic and epigenetic theories have been suggested to explain the intricacies of life and death. However, several questions remain unsettled regarding cellular death events, particularly of living tissue in the case of cancer patients, such as the fate and adaptation of cancer cells after biological death. It is possible that cancer cells can display the intent to communicate with the external environment after biological death by means of molecular, genetic, and epigenetic pathways. Whether these cancer cells contain special information in the form of coding that may help them survive beyond the biological death of cancer patients is unknown. To understand these queries in the cancer field, we hypothesize the epigenomic hard drive (EHD) as a cellular component to record and store global epigenetic events in cancerous and non-cancerous tissues of cancer patients. This mini-review presents the novel concept of EHD that is reinforced with the existing knowledge of genetic and epigenetic events in cancer. Further, we summarize the EHD understanding that may impart much potential and interest for basic and clinical scientists to unravel mechanisms of carcinogenesis, therapeutic markers, and differential drug responses.
Carcinogenesis ; Chromatin ; Clinical Coding ; Epigenomics* ; Humans

It is well established that there is a heritable element of susceptibility to chronic human ailments, yet there is compelling evidence that some components of such heritability are transmitted through non-genetic factors. Due to the complexity of reproductive processes, identifying the inheritance patterns of these factors is not easy. But little doubt exists that besides the genomic backbone, a range of epigenetic cues affect our genetic programme. The inter-generational transmission of epigenetic marks is believed to operate via four principal means that dramatically differ in their information content: DNA methylation, histone modifications, microRNAs and nucleosome positioning. These epigenetic signatures influence the cellular machinery through positive and negative feedback mechanisms either alone or interactively. Understanding how these mechanisms work to activate or deactivate parts of our genetic programme not only on a day-to-day basis but also over generations is an important area of reproductive health research.
Cues ; DNA Methylation ; Epigenomics* ; Family Characteristics ; Histone Code ; Humans ; Inheritance Patterns ; MicroRNAs ; Nucleosomes ; Reproductive Health*

PURPOSE: Cigarette smoking is a major risk factor in periodontal diseases. The pathogenesis of periodontal diseases may be affected by alterations of the inflammatory response by smoke. Nitric oxide (NO) is a gaseous, colorless, highly reactive, short-lived free radical with a pivotal role in the regulation of various physiological and pathological mechanisms in the body. It is important in host defense and homeostasis, on the one hand, whereas, on the other hand, it modulates the inflammatory response in periodontitis, leading to harmful effects. The aim of this study was to assess the levels of NO in both the serum and saliva of smokers and nonsmokers having chronic periodontitis and to compare them with periodontally healthy controls. METHODS: Sixty subjects participated in the study and were divided into three groups: group I, healthy nonsmoking subjects; group II, nonsmoking patients with chronic periodontitis; group III, smoking patients with chronic periodontitis. Each group consisted of twenty subjects. The biochemical estimation of NO in the collected serum and in the saliva was performed using the Griess colorimetric reaction. RESULTS: The results showed that the mean value of the salivary and serum NO was greater in group II than in group I, and also greater in group III than in group II. CONCLUSIONS: NO appears to play an important and rather complex role in the immuno-inflammatory process and in the remodeling and maintenance of osseous structures. It is therefore logical that modulation of this mediator has potential for the treatment of a number of inflammatory conditions including periodontal disease.
Chronic Periodontitis* ; Colorimetry ; Homeostasis ; Humans ; Nitric Oxide* ; Periodontal Diseases ; Periodontitis ; Risk Factors ; Saliva ; Smoke ; Smoking

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking.We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (–8.2 kcal/ mol) to Tubastatin A (–8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.