Variation in thoracic inlet measurements and its correlation with pulmonary dysfunction in kyphoscoliotic deformities: a prospective case-control study.

BACKGROUND: Pulmonary dysfunction in thoracic kyphoscoliosis has been correlated with chest wall distortion, uneven trunk growth and restrictive pattern. The study aims to analyse the variation in thoracic inlet measurements on pulmonary dysfunction with varying curve magnitude and thoracic cage parameters. METHODS: In a non-randomised, prospective case-control study, 80 consecutive patients with thoracic kyphoscoliosis were divided into 3 groups based on Cobb angle: Group 1 (31-50), Group 2 (51-80) and Group 3 (> 80). Thoracic inlet measurement was calculated by thoracic inlet index (TI) on MRI at the sternal level. Pulmonary function and thoracic cage parameters [hemi thorax height, rib-apex distance, AP chest diameter at sternal level and transverse thoracic diameter] were documented. TI values were compared with 20 age-matched asymptomatic controls. Multivariate correlation and regression analysis were performed to investigate the correlations. RESULTS: The mean age of the study cohort was 14.1 ± 4.4 years, including Group 1 (6 patients), Group 2 (55 patients) and Group 3 (19 patients) versus 12.9 ± 2.2 years in controls. The mean TI was 2.8 ± 0.56 in Group 1, 3.7 ± 0.9 in Group 2 and 4.0 ± 1.12 in Group 3 versus 2.6 ± 0.43 in controls. Pulmonary dysfunction was severe with TI > 7.1 (p < 0.001) in Group 3 patients with thoracic hypokyphosis. Multivariate regression for thoracic parameters and TI > 5.6 showed significant correlation of pulmonary dysfunction in Group 2 and 3 curves with apex between T1 and T4, whereas transverse thoracic diameter, rib-apex distance and hemi thorax height were weakly associated. CONCLUSION: Thoracic inlet index (TI), a neglected pre-operative variable associated with pulmonary dysfunction in thoracic kyphoscoliosis, can be evaluated on MRI without an additional cost and radiation.

C7 distal fixation anchor and its influence on sagittal profile in posterior cervical fusion; a retrospective analysis of 44 cases.

Study design: Retrospective. Purpose: In multilevel posterior cervical fusion, whether to stop distal fixation at C7 or T1, remains a matter of debate. We aimed to assess clinical feasibility of C7 as distal fixation point and sought to compare complication rates and radiological outcome between lateral mass screws and pedicle screws at C7. Overview of literature: Current literature remains inconclusive regarding need for thoracic extension of instrumentation in multilevel posterior cervical fusion. Methods: We did a retrospective review of 44 consecutive patients who underwent posterior instrumented cervical decompression and fusion for degenerative cervical myelopathy with C7 as distal fixation point, and a minimum follow-up period of two years. We had two groups of patients based on C7 instrumentation. Group 1: Lateral mass screw fixation. Group 2: Pedicle screw fixation. Primary outcome: Post-operative clinico-radiological evaluation of whole study population Secondary outcome: Comparison of complication rates and radiological outcome between groups 1 and 2. Results: Mean age was 58.06 ± 14.4 years with average follow-up duration of 35.4 ± 4.5 months. There were 18 patients in Group 1 and 26 patients in Group 2. Mean pre-operative mJOA score was 10.51 and post-operative mJOA score was 15.74 with mean recovery rate (RR) 69.82%, of which 30 patients (70.23%) had good recovery and 14 patients (29.77%) had fair recovery at final follow up. The two groups didn't show any significant difference in complication rates and outcome. Conclusion: C7 as distal fixation anchor is safe and effective in maintaining cervical sagittal balance following multilevel posterior cervical fusion. C7 lateral mass screws are found to be equally efficacious as pedicle screws in preventing worsening of sagittal profile.

Incidence of Renal Tract Abnormalities on Ultrasonography in Patients with Spinal Cord Injury: A Retrospective Pilot Study of a Military Cohort Undergoing Long-Term Institutional Rehabilitation.

STUDY DESIGN: Retrospective pilot study. PURPOSE: To assess the incidence of renal tract abnormalities using ultrasonography (US) in a military cohort with traumatic spinal cord injury (TSCI) at a tertiary level spinal cord injury center. OVERVIEW OF LITERATURE: Neurogenic bladder in TSCI patients results in significant urological morbidity. There is lack of data for these patients during the first 18 months of long-term rehabilitation in an institutional setting. METHODS: We retrospectively reviewed patient records to collect data on demographic characteristics, injury level, injury severity, time since injury, bladder management methods (such as an indwelling catheter [IC], clean intermittent catheterization [CIC], or self-voiding [S]); we correlated these data with the findings of the renal tract US. RESULTS: The study included 73 out of 81 male participants. The mean patient age was 29.99 years; the study group included 34.2% tetraplegics and 65.8% people with paraplegia. The time since injury was 6-12 months for 42.5% of the subjects and 12-18 months for 57.5% of the subjects. A normal US scan was recorded in 65.7% patients, and bladder trabeculation was the commonest finding in 15.1% of the subjects, followed by hydronephrosis (HDN) in 12.3%, and renal calculus and atrophy in 1.3% participants each. We found 22.22% of the IC group participants had higher US abnormalities than those in the reflex voiding group (statistically non-significant difference, p=0.7). Trabeculations (21.4%) and HDN (19%) were more common in those who had sustained the injury 12-18 months previously as compared to that in those who had injured themselves 6-12 months previously (p=0.04). The proportion of patients who had a normal US scan was higher in the group who sustained the injury 6-12 months previously versus those who had sustained the injury 12-18 months previously; the difference was statistically significant (p=0.02). There was no significant (p=0.72) correlation in the bladder management method, injury level, and renal tract abnormalities between the groups. CONCLUSIONS: This retrospective study shows that 65% of TSCI participants had no renal tract abnormality on US scan and bladder trabeculation ruled out as the most common finding. Long-term supervised rehabilitation may help achieve good renal quality of life; however, further prospective trials are required on this subject.

A study to analyze the pattern of synovial lesions from synovial biopsies in a tertiary care centre.

INTRODUCTION: Synovium has been documented as a primary site of inflammation and a major effector organ in a variety of joint diseases. Study of simple technique like synovial biopsy can help in early diagnosis and treatment of diseases significantly improving outcome of patient in cases of rheumatoid arthritis, osteoarthritis, etc., Only limited data exist on utility of synovial biopsies. AIM AND OBJECTIVES: To analyze the pattern of synovial lesions to differentiate between different kinds of arthritis. Also, to identify early stages of arthritis so as to prevent unnecessary invasive surgical procedure. MATERIALS AND METHODS: It's a retrospective study to analyze 103 cases of synovial lesions diagnosed in last five years at a tertiary care orthopedic center. All synovial biopsies obtained mainly by open method and few by arthroscopic method, that came to the Dept of Pathology were included. Lesions were classified into four categories that is, inflammatory joint diseases, degenerative joint diseases, tumor-like conditions and tumors. RESULTS: Age group most affected was between 61 and 70 years, with male predominance. Osteoarthritis (OA) was the most common histopathological diagnosis. Early OA tissues showed greater lining layer thickness, vessel proliferation, and inflammation, while surface fibrin deposition along with fibrosis was noted in later stages. CONCLUSION: The histo-morphological observations made in this study may have important therapeutic implications for some patients during the early evolution of arthritis and could prevent unnecessary operative intervention of later stages.

Impact of COVID-19 pandemic on orthopaedic surgeons in terms of anxiety, sleep outcomes and change in management practices: A cross-sectional study from India.

PURPOSE: The aim of this study was to assess the effects of the COVID-19 pandemic on anxiety, sleep outcomes and change in clinical management practices among orthopaedic surgeons following a nation-wide lockdown. METHODS: We conducted an online cross-sectional study using piloted structured questionnaires with self-reported responses from Indian orthopaedic surgeons. Study participants were identified through social networking sites: Facebook and WhatsApp. The extent of anxiety and sleep quality was assessed by the standardised seven-item Generalised Anxiety Disorder (GAD-7) scale, single-item sleep quality scale, questions on unavailability of personal protective equipment, training module on COVID-19 and change in orthopaedic patient management. RESULTS: One hundred male orthopaedic surgeons responded to the survey with majority (79%) in 30-44 years age group. Severe anxiety scores were observed in 8%; moderate, mild and minimal anxiety was observed in 12%, 27% and 53% surgeons respectively. Changes in management practice due to the pandemic was admitted by 65% respondents. We also observed an association between higher anxiety among surgeons and primary or secondary level of healthcare facility: (p = 0.04). Sleep disturbance was significantly associated with change in management practice to non-operative procedures (p = 0.03). CONCLUSION: Anxiety among orthopaedic surgeons during the COVID-19 pandemic is related to factors like younger age group, working in a primary or secondary healthcare facility. Early recognition of anxiety is essential to prevent serious psychological sequelae.

Thirty-Six-Month Follow-up of Diaphragm Pacing with Phrenic Nerve Stimulation for Ventilator Dependence in Traumatic Tetraplegia: The Way Forward for Spinal Cord Injury Rehabilitation in a Developing Country.

Respiratory failure and chronic ventilator dependence in tetraplegics following cervical injuries located high on the spine (C1-C3) constitute significant challenges in the rehabilitation of patients given the occurrence of repeated hospitalizations and an ever-increasing financial burden. A 30-year-old man presented with posttraumatic tetraplegia following an unstable injury at the C1-C2 level with cord compression; he was managed by posterior stabilization and decompression followed by ventilator dependence and no rehabilitation until 6 months postinjury. We implanted phrenic nerve stimulator electrodes bilaterally for indirect diaphragm pacing by an implantable pulse generator that allowed for weaning from mechanical ventilation and spontaneous ventilator-free breathing at 20 weeks post-implantation and which facilitated post-tetraplegia rehabilitation. At 36 months after implantation, the patient is ventilator-free without any procedure-related complications or respiratory infections. Diaphragm pacing with phrenic nerve stimulation may be a way forward for ventilator-dependent tetraplegics in developing countries to pursue effective rehabilitation and improved quality of life.

Anxiety and Sleep Disturbances Among Health Care Workers During the COVID-19 Pandemic in India: Cross-Sectional Online Survey.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has become a serious concern among the global medical community and has resulted in an unprecedented psychological impact on health care workers, who were already working under stressful conditions. OBJECTIVE: In this study, we aimed to evaluate and measure the effects of the COVID-19 pandemic on the anxiety levels and sleep quality among health care workers in India, as well as to determine how the unavailability of personal protective equipment affects their willingness to provide patient-related care. METHODS: We conducted an online cross-sectional study using piloted, structured questionnaires with self-reported responses from 368 volunteer male and female health care workers in India. Study participants were identified through social networking platforms such as Facebook and WhatsApp. The survey evaluated the participants' degree of signs and symptoms of anxiety and sleep quality based on the 7-item Generalized Anxiety Disorder (GAD-7) scale and single-item Sleep Quality Scale, respectively. Information on the availability of personal protective equipment was collected based on responses to relevant survey questions. RESULTS: The majority of health care workers (126/368, 34.2%) were in the age group 45-60 years, and 52.2% (192/368) were doctors. Severe anxiety (ie, GAD-7 score >10) was observed among 7.3% (27/368) health care workers, whereas moderate, mild, and minimal anxiety was observed among 12.5% (46/368), 29.3% (108/368), and 50.8% (187/368) health care workers, respectively. Moreover, 31.5% (116/368) of the health care workers had poor-to-fair sleep quality (ie, scores <6). Univariate analysis showed female gender and inadequate availability of personal protective equipment was significantly associated with higher anxiety levels (P=.01 for both). Sleep disturbance was significantly associated with age <30 years (P=.04) and inadequate personal protective equipment (P<.001). Multivariable analysis showed that poorer quality of sleep was associated with higher anxiety levels (P<.001). CONCLUSIONS: The COVID-19 pandemic has potentially caused significant levels of anxiety and sleep disturbances among health care workers, particularly associated with the female gender, younger age group, and inadequate availability of personal protective equipment. These factors put health care workers at constant risk of contracting the infection themselves or transmitting it to their families. Early identification of at-risk health care workers and implementation of situation-tailored mitigation measures could help alleviate the risk of long-term, serious psychological sequelae as well as reduce current anxiety levels among health care workers.

Does preventive care bundle have an impact on surgical site infections following spine surgery? An analysis of 9607 patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The purpose was to analyze the effect of care bundle protocol on SSI in our institution. Postoperative surgical site infections (SSI) pose significant health burden. In spite of the use of prophylactic antibiotics, surgical advances and postoperative care, wound infection continues to affect patient outcomes after spine surgery. METHODS: Retrospective analysis of 9607 consecutive patients who underwent spine procedures from 2014 to 2018 was performed. Preventive care bundle was implemented from January 2017 consisting of (a) preoperative bundle-glycemic control, chlorhexidine gluconate (CHG) bath, (b) intra-operative bundle-time specified antibiotic prophylaxis, CHG+ alcohol-based skin preparation (c) postoperative bundle-five moments of hand hygiene, early mobilization and bundle auditing. Patients operated from January 2017 were included in the post-implementation cohort and prior to that the pre-implementation cohort was formed. Data were drawn from weekly and yearly spine audits from the hospital infection committee software. Infection data were collected based on CDC criteria, further sub classification was done based on procedure, spinal disorders and spine level. Variables were analyzed and level of significance was set as < 0.05. RESULTS: A total of 7333 patients met the criteria. The overall SSI rate decreased from 3.42% (131/3829) in pre-implementation cohort to 1.22% (43/3504, p = 0.0001) in post-implementation cohort (RR = 2.73, OR = 2.79). Statistically significant reduction was seen in all the groups (a) superficial and deep, (b) early and late and (c) instrumented and uninstrumented groups but was more pronounced in early (p = 0.0001), superficial (p = 0.0001) and instrumented groups (p = 0.0001). On subgroup analysis based on spine level and spinal disorders, significant reduction was seen in lumbar (p = 0.0001) and degenerative group (p = 0.0001). CONCLUSIONS: Our study revealed significant reduction of SSI secondary to strict bundle adherence and monitored compliance compared to patients who did not receive these interventions. LEVEL OF EVIDENCE: III.

Unplanned Readmissions after Spine Surgery: A Single-Center Prospective Analysis of a 90-Day Model in 2,860 Cases.

STUDY DESIGN: Prospective study. PURPOSE: During the last decades, an emergence of unplanned readmissions has been shown to be a useful tool to gage the healthcare quality and hospital performance. Previous studies were limited by their retrospective designs based on database information and short-term 30-day follow-up intervals. We analyzed the incidence and causes for unplanned readmissions following spine surgery at a 90-day interval and the difference at 30-, 31-60-, and 61-90-day intervals after discharge. Additionally, we assessed total beddays lost and the economic impact of readmissions and probable risk factors. OVERVIEW OF LITERATURE: Recent reports on readmission rates suggested the contribution of this parameter for the assessment of healthcare quality. METHODS: A prospective analysis of 2,860 admissions was performed over 1 year in a tertiary care orthopedic hospital. All unscheduled readmissions following spine surgery within 90 days of discharge were included, irrespective of type or location of surgery. Polytrauma, primary osseous infections, and planned readmissions were excluded. RESULTS: Our readmission rate was 3.32% (95/2,860). Leading readmission causes were surgical site infections (SSIs) accounting for 44.21% (n=42; superficial, 23; deep, 11; organ and space, 8), followed by aseptic pain 31.58% (n=30) and medical causes 13.68% (n=13). Though 86.95% of superficial SSIs occurred within 30 days, 21.1% of deep SSIs occurred beyond 30 days. During the 30-90-day interval, 33.68% of readmissions occurred. The financial burden amounted to 41,93,660 Indian Rupees, and the mean bed-days lost was 7.33 per readmission. Hospital stay ≥10 days, health insurance, and comorbid illnesses (diabetes, hypertension, and liver disease) were associated with readmissions (p<0.05). CONCLUSIONS: Our study showed that SSIs and aseptic pain were the leading causes of readmissions at 90 days after spine surgery. Limiting the analysis to 30-day readmissions as in previous studies would lead to failure in the identification of more severe complications like deep SSIs. Continued vigilance, particularly for patients with predisposing factors, could help alleviate the financial burden.

Prognostic utility of magnetic resonance imaging (MRI) in predicting neurological outcomes in patients with acute thoracolumbar spinal cord injury.

PURPOSE: Utility of MRI for predicting neurological outcomes in acute cervical spinal cord injury (SCI) is well established but its value in thoracolumbar (TL) SCI needs to be evaluated. METHODS: Seventy-six patients operated for acute TL spinal injuries between January 2014 and March 2016 were reviewed to obtain demographic details, neurology at admission and at the final follow-up. Patients were divided based on the neurology at presentation into group 1 (ASIA A), group 2 (ASIA B, C, D) and group 3 (normal neurology). Preoperative MRI and CT scans were evaluated to measure parameters like osseus canal compromise, spinal cord compression (SCC), spinal cord swelling, length of cord swelling (LOS), length of edema (LOE) and the presence of hemorrhage. The MRI parameters were compared between the groups for their predictive value of neurology on admission and at the final follow-up. RESULTS: Of the 38 patients in group 1, six patients recovered by 1 grade, nine patients recovered by 2 grades and there was no recovery in 23 (60.5%) patients. Among group 2 patients, nine (40.9%) out of 22 recovered to ASIA E neurology. On univariate analysis, SCC (P = 0.009), LOS (P = 0.021) and length of edema (P = 0.002) were associated with complete neurological deficit at presentation. However, on multivariate regression analysis only LOE was significant (P = 0.007) in predicting neurology at admission and at follow-up. CONCLUSION: Greater the rostrocaudal LOE, worse is the neurology at presentation, and it is associated with poor neurological recovery at follow-up. These slides can be retrieved under Electronic Supplementary Material.

Detection of DNA Double-Strand Breaks Using Pulsed-Field Gel Electrophoresis.

DNA is one of the most biologically important targets of exogenous and endogenous toxicants as well as carcinogens. Damage to DNA can be of different types (e.g., DNA adducts, DNA protein cross-links, single-strand breaks, oxidized bases, abasic sites, and double-strand breaks (DSBs)). DSBs are considered the most lethal form of DNA damage for eukaryotic cells, and if left unrepaired or misrepaired, can cause cell death, chromosome instability, and cancer. DSBs can arise in the cells through different sources and can be distinguished as endogenous or exogenous DSBs. Exogenous sources can be chemotherapeutic drugs, irradiation, and environmental chemicals. The endogenous causes of DNA DSBs in the cells are mainly reactive oxygen species and faulty repair of oxidative clustered DNA lesions. Qualitative and quantitative analysis of DNA DSBs is of utmost importance to understand physiologically relevant cellular processes as well as to investigate the genotoxic or clastogenic effects of toxicants. Pulsed-field gel electrophoresis (PFGE) is a widely used method for direct quantification of DNA DSBs. In this method, the cells exposed to DSB-inducing agents are embedded in the agarose blocks and lysed. These agarose blocks containing DNA are then run under multiple electric fields which are at 120° angle, to aid in the movement of large DNA strands. It gives a direct and specific measure of DSBs unlike the foci-based assays. This chapter provides a brief overview of the various commonly used approaches to analyze DNA DSBs and describes the theory, advantages and method of PFGE, for use in cells exposed to DNA DSB inducing agents.

TiO2 NPs Induce DNA Damage in Lymphocytes from Healthy Individuals and Patients with Respiratory Diseases-An Ex Vivo/In Vitro Study.

Little is known of the effects of nanoparticles in human systems, let alone in diseased individuals and nanotechnology has preceded nanotoxicology. Therefore, the effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases [lung cancer, chronic obstructive pulmonary disease (COPD) and asthma] were compared with those in healthy Individuals, to determine differences in sensitivity to nanochemical insult. The Comet assay was performed according to recommended guidelines. The micronucleus assay and ras oncoprotein detection were conducted according to published standard methods. The results showed statistically significant concentration-dependent genotoxic effects of TiO2 NPs in both respiratory patient and control groups in the Comet assay. The TiO2 NPs caused DNA damage in a concentration dependent manner in both groups (respiratory and healthy controls) with the exception of the lowest TiO2 concentration (10 µg/ml) which did not induce significant damage in healthy controls (n.s). When OTM data were used to compare the whole patient group and the control group, the patient group had more DNA damage (p > 0.001) with the exception of 10 µg/ml of TiO2 that caused less significant damage to patient lymphocytes (p < 0.05). Similarly, there was an increase in the pattern of cytogenetic damage measured in the MN assay without statistical significance except when compared to the negative control of healthy individuals. Furthermore, when modulation of ras p21 expression was investigated, regardless of TiO2 treatment, only lung cancer and COPD patients expressed measurable ras p21 levels. Results were achieved in the absence of cytotoxicity.

Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes.

Endogenous formaldehyde is abundantly present in our bodies, at around 100 µM under normal conditions. While such high steady state levels of formaldehyde may be derived by enzymatic reactions including oxidative demethylation/deamination and myeloperoxidation, it is unclear whether endogenous formaldehyde can initiate and/or promote diseases in humans. Here, we show that fluorescent malondialdehyde-formaldehyde (M2FA)-lysine adducts are immunogenic without adjuvants in mice. Natural antibody titers against M2FA are elevated in atherosclerosis-prone mice. Staining with an antibody against M2FA demonstrated that M2FA is present in plaque found on the aortic valve of ApoE -/- mice. To mimic inflammation during atherogenesis, human myeloperoxidase was incubated with glycine, H2O2, malondialdehyde, and a lysine analog in PBS at a physiological temperature, which resulted in M2FA generation. These results strongly suggest that the 1,4-dihydropyridine-type of lysine adducts observed in atherosclerosis lesions are likely produced by endogenous formaldehyde and malondialdehyde with lysine. These highly fluorescent M2FA adducts may play important roles in human inflammatory and degenerative diseases.

Poor recognition of O6-isopropyl dG by MGMT triggers double strand break-mediated cell death and micronucleus induction in FANC-deficient cells.

Isopropyl methanesulfonate (IPMS) is the most potent genotoxic compound among methanesulfonic acid esters. The genotoxic potential of alkyl sulfonate esters is believed to be due to their alkylating ability of the O6 position of guanine. Understanding the primary repair pathway activated in response to IPMS-induced DNA damage is important to profile the genotoxic potential of IPMS. In the present study, both chicken DT40 and human TK6 cell-based DNA damage response (DDR) assays revealed that dysfunction of the FANC pathway resulted in higher sensitivity to IPMS compared to EMS or MMS. O6-alkyl dG is primarily repaired by methyl guanine methyltransferase (MGMT), while isopropyl dG is less likely to be a substrate for MGMT. Comparison of the cytotoxic potential of IPMS and its isomer n-propyl methanesulfonate (nPMS) revealed that the isopropyl moiety avoids recognition by MGMT and leads to higher cytotoxicity. Next, the micronucleus (MN) assay showed that FANC deficiency increases the sensitivity of DT40 cells to MN induction by IPMS. Pretreatment with O6-benzyl guanine (OBG), an inhibitor of MGMT, increased the MN frequency in DT40 cells treated with nPMS, but not IPMS. Lastly, IPMS induced more double strand breaks in FANC-deficient cells compared to wild-type cells in a time-dependent manner. All together, these results suggest that IPMS-derived O6-isopropyl dG escapes recognition by MGMT, and the unrepaired DNA damage leads to double strand breaks, resulting in MN induction. FANC, therefore, plays a pivotal role in preventing MN induction and cell death caused by IPMS.

Oxidative stress at low levels can induce clustered DNA lesions leading to NHEJ mediated mutations.

DNA damage and mutations induced by oxidative stress are associated with various different human pathologies including cancer. The facts that most human tumors are characterized by large genome rearrangements and glutathione depletion in mice results in deletions in DNA suggest that reactive oxygen species (ROS) may cause gene and chromosome mutations through DNA double strand breaks (DSBs). However, the generation of DSBs at low levels of ROS is still controversial. In the present study, we show that H2O2 at biologically-relevant levels causes a marked increase in oxidative clustered DNA lesions (OCDLs) with a significant elevation of replication-independent DSBs. Although it is frequently reported that OCDLs are fingerprint of high-energy IR, our results indicate for the first time that H2O2, even at low levels, can also cause OCDLs leading to DSBs specifically in G1 cells. Furthermore, a reverse genetic approach revealed a significant contribution of the non-homologous end joining (NHEJ) pathway in H2O2-induced DNA repair & mutagenesis. This genomic instability induced by low levels of ROS may be involved in spontaneous mutagenesis and the etiology of a wide variety of human diseases like chronic inflammation-related disorders, carcinogenesis, neuro-degeneration and aging.

Hook plate fixation for acute acromioclavicular dislocations without coracoclavicular ligament reconstruction: a functional outcome study in military personnel.

The aim of our study was to evaluate the shoulder function after clavicular hook plate fixation of acute acromioclavicular dislocations (Rockwood type III) in a population group consisting exclusively of high-demand military personnel. This prospective study was carried out at a tertiary care military orthopaedic centre during 2012-2013 using clavicular hook plate for management of acromioclavicular injuries without coracoclavicular ligament reconstruction in 33 patients. All patients underwent routine implant removal after 16 weeks. The functional outcome was assessed at 3, 6 and 12 months after hook plate removal and 2 years from the initial surgery using the Constant Murley and UCLA Scores. All the patients were male serving soldiers and had sustained acromioclavicular joint dislocation (Rockwood type III). Mean age of the patient group was 34.24 years (21-55 years). The mean follow-up period in this study was 23.5 months (20-26 months) after hook plate fixation and an average of 19.9 months (17-22 months) after hook plate removal. The average Constant Score at 3 months after hook plate removal was 60.3 as compared to 83.7 and 90.3 at 6 months and 1 year, respectively, and an average of 91.8 at the last follow-up that was approximately 2 years after initial surgery which was statistically significant (p value <0.05). The UCLA Score was an average of 15.27, 25.9 and 30.1 at 3, 6 months and 1 year, respectively, after removal of hook plate which improved further an average of 32.3 at the last follow-up, which was also statistically significant (p value <0.05). Clavicular hook plate fixation without coracoclavicular ligament reconstruction is a good option for acute acromioclavicular dislocations producing excellent medium-term functional results in high-demand soldiers.

The endogenous exposome.

The concept of the Exposome is a compilation of diseases and one's lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the endogenous exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions.

Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells.

For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O(6)-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D3]-methylnitrosourea. Endogenous amounts of both adducts remained nearly constant, while the exogenous adducts showed linear dose-responses. The data show that O(6)-methyl-dG adducts ≥1.8/10(8) dG correlated with published studies that demonstrated significant increases of mutations under these conditions. The combined results do not support linear extrapolations to zero when data are available for science-based regulations.

Methods for detection of oxidative stress and genotoxicity of engineered nanoparticles.

The distinctive characteristics of engineered nanoparticles (ENPs) such as higher surface-to-volume ratio find immense applications in personal care products, food packaging, drug delivery systems, therapeutics & biosensors and others. The exponential increase in the ENP containing consumer products in the last 5 years has also increased their inadvertent release in the environment and a debate towards their adverse effects to the human and environment health. A variety of ENPs with different size, shape, and surface properties have been shown to induce genotoxicity, cytotoxicity, and oxidative stress in different cellular models. Here we describe the techniques and protocols used in the assessment of the genotoxicity (single-cell gel electrophoresis (comet) assay, cytokinesis block micronucleus assay) and oxidative stress parameters (reactive oxygen species, lipid peroxidation, and glutathione depletion) induced by the ENPs in the cells.