Experience of an anatomic femoral stem in a UK orthopaedic centre beyond 20 years of follow-up.

INTRODUCTION: Increasing interest in the use of anatomical stems has developed as the prevalence of periprosthetic fractures (PPFs) continues to increase. The primary aim of this study was to determine the long-term survivorship and PPF rate of an anatomical femoral stem in a single UK centre. PATIENTS AND METHODS: Between 2000 and 2002, 94 consecutive THAs were performed using the 170 mm Lubinus SP II anatomical femoral stem in our institution. Patient demographics, operative details and clinical outcomes were collected prospectively in an arthroplasty database. Patient records and national radiographic archives were reviewed finally at a mean of 21.5 years (SD 0.7) following surgery to identify occurrence of subsequent revision surgery, dislocation or periprosthetic fracture. RESULTS: Mean patient age at surgery was 65.8 years (SD 12.5, 34-88 years). There were 48 women (51%). Osteoarthritis was the operative indication in 88 patients (94%). Analysis of all-cause THA failure demonstrated a survivorship of 98.5% (95% confidence interval [CI], 98.0-99.3%) at 10 years and 96.7% (94.5-98.9%) at 21 years. The 20-year stem survival for aseptic loosening was 100% with no cases of significant lysis found (lucent line > 2 mm) and no stems required revision. Patient demographics did not appear to influence risk of revision (p > 0.05). There were 2 revisions in total (2 for acetabular loosening with original stems retained). There were no PPFs identified at mean 21.5 year follow-up and 5 dislocations (5%). CONCLUSIONS: The Lubinus SP II 170 mm stem demonstrated excellent survivorship and negligible PPF rates over 20 years following primary THA.

A stochastic regularized second-order iterative scheme for optimal control and inverse problems in stochastic partial differential equations.

Numerous applied models used in the study of optimal control problems, inverse problems, shape optimization, machine learning, fractional programming, neural networks, image registration and so on lead to stochastic optimization problems in Hilbert spaces. Under a suitable convexity assumption on the objective function, a necessary and sufficient optimality condition for stochastic optimization problems is a stochastic variational inequality. This article presents a new stochastic regularized second-order iterative scheme for solving a variational inequality in a stochastic environment where the primary operator is accessed by employing sampling techniques. The proposed iterative scheme, which fits within the general framework of the stochastic approximation approach, has its almost-sure convergence analysis given in a Hilbert space. We test the feasibility and the efficacy of the proposed stochastic approximation approach for a stochastic optimal control problem and a stochastic inverse problem, both associated with a second-order stochastic partial differential equation. This article is part of the theme issue 'Non-smooth variational problems and applications'.

The 100 Citation Classics in the Irish Medical Literature; A Bibliometric Analysis.

Identifying citation classics is a valuable metric of research performance. Ireland has a distinguished history of medical research, although Ireland's top-cited articles are unknown. The SCOPUS database identified all medical and surgical articles published by journals in the Republic of Ireland or Northern Ireland. The 100 top-cited articles were analysed. The most cited article received 240 citations. There is an observed trend of increasing number of authors over time (p<0.05). General medicine and public health are the most common topics. The majority of works originate from Irish institutions. Collaborative research and non-Irish research are poorly represented among the citation classics. The Irish medical literature contains multiple highly cited and influential articles.

Mutational and phenotypic spectra of KCNE1 deficiency in Jervell and Lange-Nielsen Syndrome and Romano-Ward Syndrome.

KCNE1 encodes a regulatory subunit of the KCNQ1 potassium channel-complex. Both KCNE1 and KCNQ1 are necessary for normal hearing and cardiac ventricular repolarization. Recessive variants in these genes are associated with Jervell and Lange-Nielson syndrome (JLNS1 and JLNS2), a cardio-auditory syndrome characterized by congenital profound sensorineural deafness and a prolonged QT interval that can cause ventricular arrhythmias and sudden cardiac death. Some normal-hearing carriers of heterozygous missense variants of KCNE1 and KCNQ1 have prolonged QT intervals, a dominantly inherited phenotype designated Romano-Ward syndrome (RWS), which is also associated with arrhythmias and elevated risk of sudden death. Coassembly of certain mutant KCNE1 monomers with wild-type KCNQ1 subunits results in RWS by a dominant negative mechanism. This paper reviews variants of KCNE1 and their associated phenotypes, including biallelic truncating null variants of KCNE1 that have not been previously reported. We describe three homozygous nonsense mutations of KCNE1 segregating in families ascertained ostensibly for nonsyndromic deafness: c.50G>A (p.Trp17*), c.51G>A (p.Trp17*), and c.138C>A (p.Tyr46*). Some individuals carrying missense variants of KCNE1 have RWS. However, heterozygotes for loss-of-function variants of KCNE1 may have normal QT intervals while biallelic null alleles are associated with JLNS2, indicating a complex genotype-phenotype spectrum for KCNE1 variants.

Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an indicator of apoptosis, showed that MLH1 translocation only occurred in MMR proficient (SW480) cells upon induction of apoptosis further suggested a MSH2 dependent role of MLH1 in apoptosis. These data suggest a role of MLH1 in mediation of apoptosis in a MSH2-dependent manner. Taken together, our data supported an interdependence of mismatch repair proteins, particularly MLH1 and MSH2, in the mediation of apoptosis in human colorectal carcinoma cell lines.

WITHDRAWN: MUA with steroid injection vs. arthroscopic capsular release for adhesive capsulitis: A prospective randomised study.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Depression in patients with idiopathic pulmonary fibrosis.

Depression carries enormous global morbidity and is 1.5-7 times likelier to occur in individuals with chronic illness than in the general population. Idiopathic pulmonary fibrosis (IPF) has a rising incidence with a severe impact on quality of life. An indication of the prevalence of depression in this group is therefore of paramount interest. A prospective study was performed. A total of 118 participants with IPF who attended the interstitial lung disease clinic in Ninewells Hospitals, Dundee, Scotland, from May 2010 to September 2011 were recruited. Informed consent was obtained. The male to female ratio was 60:58. The Wakefield Self-assessment of Depression Inventory was used (scores ≥15 denote a depressed state). Pulmonary function tests were measured to correlate disease severity with depression scores. Of them, 58 patients had significant depressive symptoms scoring ≥15; only nine were taking antidepressant medication. The mean depression score of female participants was 15.0 ± 0.77 (SD 5.9), compared with a mean male score of 13.1 ± 0.99 (SD 7.5). Disease severity, age, duration since diagnosis and number of co-morbidities were not significantly correlated with depression. The study population had a high prevalence of depressive symptoms. Medical therapy for pulmonary fibrosis is limited and therefore palliation of symptoms and pulmonary rehabilitation form the main strategy for management. Depression should be actively screened in patients with IPF.

Detection of toxic metals (lead and chromium) in talcum powder using laser induced breakdown spectroscopy.

A laser induced breakdown spectroscopic (LIBS) system was developed using a 266 nm laser and a high-resolution spectrograph (Andor SR 500 i-A) to detect the trace levels of the highly toxic metals such as lead and chromium present in different brands of talcum powder available in the local market. The strongest atomic transition lines of lead (Pb) (405.7 nm) and chromium (Cr) (425.4 nm) were used as spectral markers to simultaneously detect lead and chromium. The LIBS system was calibrated for these two heavy metals, and the system was able to detect 15-20 parts per million (ppm) of lead and 20-30 ppm of chromium in the talcum powder sample. The limits of detection of the LIBS system were also estimated, and they are 1.96 and 1.72 ppm per million respectively for lead and chromium. This study is highly significant due to the use of cosmetic products that could affect the health of millions of people around the globe.

Expression analysis of hepatic mitochondria-related genes in mice exposed to acrylamide and glycidamide.

Acrylamide (AA) is an industrial chemical that has been extensively investigated for central nervous system (CNS), reproductive, and genetic toxicity. However, AA effects on the liver, a major organ of drug metabolism, have not been adequately explored. In addition, the role of mitochondria in AA-mediated toxicity is still unclear. Changes in expression levels of genes associated with hepatic mitochondrial function of male transgenic Big Blue (BB) mice administered 500 mg/L AA or an equimolar concentration (600 mg/L) of its reactive metabolite glycidamide (GA) in drinking water for 3 and 4 wk, respectively, were examined. Transcriptional profiling of 542 mitochondria-related genes indicated a significant downregulation of genes associated with the 3-beta-hydroxysteroid dehydrogenase family in AA- and GA-treated mice, suggesting a possible role of both chemicals in altering hepatic steroid metabolism in BB mice. In addition, genes associated with lipid metabolism were altered by both treatments. Interestingly, only the parental compound (AA) significantly induced expression levels of genes associated with oxidative phosphorylation, in particular ATP synthase, which correlated with elevated ATP levels, indicating an increased energy demand in liver during AA exposure. Acrylamide-treated mice also showed significantly higher activity of glutathione S-transferase in association with decreased levels of reduced glutathione (GSH), which may imply an enhanced rate of conjugation of AA with GSH in liver. These results suggest different hepatic mechanisms of action of AA and GA and provide important insights into the involvement of mitochondria during their exposures.

The benefits of dual-consultant operating in complex breast reconstruction: A retrospective cohort comparison study.

BACKGROUND: Dual-consultant operating (DCO) has been introduced in a multitude of surgical specialities. This retrospective cohort comparison study seeks to delineate any benefits DCO may confer on list utilisation, patient safety and training opportunities. METHODS: A retrospective cohort comparison of all free-flap breast reconstruction cases conducted at a single centre by five consultant plastic surgeons in the period May 2016-May 2020. RESULTS: A total of 281 patient records were used for analysis; 146 cases were dual consultants compared with 135 single consultants, representing 186 and 158 free flaps, respectively. Patient demographics were near identical in terms of patient age, BMI and ASA grade. Operating times were significantly reduced for both unilateral (mean reduction 59.49 min) and bilateral cases (mean reduction 38.14 min) with the presence of dual consultants. The mean length of stay for dual-consultant cases was on average 0.35 days less than for single consultant cases (p = 0.04). Dual-consultant case complications were less severe than those of single consultant cases (mean Clavien-Dindo severity 1.35 vs 0.96, p = 0.05). The rates of trainee one-to-one consultant training were increased in dual-consultant cases when preparing vessels (0.08 vs 0.35, p=<0.01) and performing anastomosis (0.63 vs 0.77, p = 0.03). CONCLUSIONS: DCO for complex breast reconstruction confers significant benefits to operating time, list utility and patient safety whilst protecting training opportunities for trainees. Plastic surgery departments looking to redesign services in the post-SARS-CoV-19 era should consider its adoption into their enhanced recovery protocols.

Oral glucosamine increases expression of transforming growth factor ß1 (TGFß1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity.

Glucosamine is used for alleviating pain in osteoarthritis. Clinical trials have reported that glucosamine has equivocal efficacy. Glucosamine is also used in cell cultures to stimulate hexosamine flux and protein O-glycosylation, but at many-fold greater concentrations than those in human plasma following oral dosing. Lean Zucker rats were dosed orally for 6 weeks with glucosamine hydrochloride at doses (0-600 mg/kg/day) that produced peak serum concentrations of <1-35 µM, spanning the human exposure range. Relative expression of both TGFß1 and CTGF mRNA were significantly increased up to 2.3-fold in liver, kidney and articular cartilage when evaluated 4h after final dose. Apparent threshold serum glucosamine (C(max)) concentration required to increase TGFß1 expression in cartilage was 10-20 µM. These increases were associated with significant increases in UDP-N-acetylglucosamine concentrations suggesting increased hexosamine flux. Both TGFß1 and CTGF are mediators of chondrocyte proliferation and cartilage repair. Study demonstrates that oral glucosamine doses that produce clinically relevant serum glucosamine concentrations can induce tissue TGFß1 and CTGF expression in vivo and provides a mechanistic rationale for reported beneficial effects of glucosamine therapy. Induction of renal TGFß1 and CTGF mRNA suggests that potential sclerotic side-effects may occur following consumption of potent glucosamine preparations.

Selective radiosensitization of p53-deficient cells by caffeine-mediated activation of p34cdc2 kinase.

The induction of tumor cell death by anticancer therapy results from a genetic program of autonomous cell death termed apoptosis. Because the p53 tumor suppressor gene is a critical component for induction of apoptosis in response to DNA damage, its inactivation in cancers may be responsible for their resistance to genotoxic anticancer agents. The cellular response to DNA damage involves a cell-cycle arrest at both the G1/S and G2/M transitions; these checkpoints maintain viability by preventing the replication or segregation of damaged DNA. The arrest at the G1 checkpoint is mediated by p53-dependent induction of p21WAF1/CIP1, whereas the G2 arrest involves inactivation of p34cdc2 kinase. Following DNA damage, p53-deficient cells fail to arrest at G1 and accumulate at the G2/M transition. We demonstrate that abrogation of G2 arrest by caffeine-mediated activation of p34cdc2 kinase results in the selective sensitization of p53-deficient primary and tumor cells to irradiation-induced apoptosis. These data suggest that pharmacologic activation of p34cdc2 kinase may be a useful therapeutic strategy for circumventing the resistance of p53-deficient cancers to genotoxic anticancer agents.

Inactivation of Different Salmonella enteriditis Phage Types and Safety and Efficacy of Inactivated Products in Chicken.

This study was conducted to inactivate Salmonella enteriditis phage types (SE pt) and to determine the safety and efficacy of inactivated SE pt in chickens. SE pt 1, 3A, 6A, 7, and 35 were inactivated and inoculated (0.20 mL) in 124 chickens divided into 6 groups (CV1, CV3A, CV6A, CV7, CV35, and CV0 as a control). Sampling was conducted on day 14 after inoculation (pi). Eight chickens from each group were separated on day 14 pi for oral challenge with 0.20 mL/chicken (1010 cfu/mL) SE pt 6A and designated CV1C, CV3AC, CV6AC, CV7C, CV35C, and CV0C as control chickens. On days 7 and 14 postchallenge (pc), 4 chickens from every group were sacrificed for sampling. There was no significant difference in the body weight between different groups. In challenged groups, there was no significant association between different tissues and isolation of Salmonella on days 7 and 14 pc. There was significance (p < 0.05) in isolation of Salmonella when CV0C group was compared with other challenged groups. Significance was not observed between different tissues with respect to induction of microscopic changes. Significance was not observed between day 7 pc and day 14 pc with respect to scoring of lesions induced. Clinical signs and gross lesions were also recorded. ELISA was applied. Only in CV3AC group, the mean antibody titer was 1359 on day 14 pc. The conclusion was that inactivated SE pt 3A and 6A were safe and efficacious for protection against Salmonella enteriditis infection in chickens.

Identification and crop damage assessment of indian crested porcupine (Hystrix indica) in selected zones of Abbottabad, Pakistan.

Indian crested porcupine is the largest rodent pest that damages a wide variety of crops, vegetables, and tree species which ultimately causes huge economic loss in Pakistan, which is an agricultural country. It prefers to live in hilly terrain but common in temperate and tropical forests, shrublands, and grasslands. This study focused on the identification and assessment of crops damaged along with the main precautionary measures used by the local farmers. The data was collected from twenty-four villages of two union councils i.e. Chamhad and Slahad of district Abbottabad. Two types of data (primary and secondary) were collected from the study area. Primary data was collected for identification and estimation calculation of total crop damaged through direct field observation by taking random quadrates in each village of the study area. The damage in the crop was assessed by randomly selecting a quadrate of 1x1 m2 for the wheat, pearl millet, and Sorghum fields. While 4x4 m2 quadrates were taken for maize and vegetables. At least three quadrate samples were taken from each field including one quadrate taken from the center of the field area. In union council Chamhad, damage to maize (11.31%) and wheat (0.73%) by the Indian crested porcupine while in union council Salhad, damage of maize (6.95%) and wheat (1.6%) was observed. In the entire study area, overall damage to maize crop (8.01%) and wheat (0.88%) was calculated. Based on information obtained from the farmers, the Indian porcupine inflicted damage to potato, tomato, cauliflower, chili pepper, turnip, radish, pea, and onion, etc. Secondary data obtained through a questionnaire survey to explore the human porcupine conflict and precautionary measures used by the farmers and landowners. Open and close-ended questionnaires (159) highlighted the presence of Indian crested porcupine in the study area and 96% of the respondents have seen porcupine directly. Many types of precautionary measures were used by the farmers such as fencing, night stay, night firing, and dogs to decrease the crop damage, respondents (63.91%) use guns for hunting. however, due to the largely agricultural area and nocturnal behavior of Indian crested porcupine majority of the respondents (51.57%) did not use any precautionary measure. Biological control of Indian porcupine is recommended in the study area. Farmers should be encouraged and provide incentives and killing through current should be banned while proper hunting license should be issued to overcome overhunting. Scientific studies are required to control the reproduction of porcupine specifically in the more damaged areas.

Payment for ecosystem services (PES): a holistic tool for sustainable forest management-a case study from Pakistan.

Economic valuation of ecosystem services is a new concept in forest management. Economic valuation provides basis for payment for ecosystem services (PES). Therefore, objective of this study was to evaluate eco-tourism and carbon stock services of the Maindam valley, District Swat, Pakistan. For the carbon stock calculation, a sample size of 155 plots of 0.1 hectare (Ha) was taken using preliminary survey at 95% confidence interval and 10% allowable error. The data for tourism services was collected from owners of all the hotels, 100 tourists and key informants of the area at 10% sampling intensity on pretested questionnaire for twenty years period (1997-2017). Results showed that Miandam valley has carbon stock worth US$ 16,306,000 while the value of eco-tourism was US$ 1,578,458 on annual basis. The results also showed that trend of tourism has drastically declined after the 9/11 incident for foreigners and locals and the situation was further deteriorated during the era of Talibanization or militancy from 2008-2011. This study recommends implementation of PES strategy at the rate of 5%, thus a total of US$ 78,922 can be earned from eco-tourism and carbon crediting in the study area annually, which could play important role in sustainable forest management.

Major threats and habitat use status of Demoiselle crane (Anthropoides virgo), in district Bannu, Pakistan.

Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.

Forest yield prediction under different climate change scenarios using data intelligent models in Pakistan.

This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.

Transcatheter closure of a patent ductus arteriosus in a patient with an anomalous inferior vena cava.

A patient with a patent ductus arteriosus (PDA) was catheterized for device closure. Anomalous systemic venous drainage was found with interrupted inferior vena cava and persistence of hepatic vessel plexus. Using the superior vena cava route, the PDA was closed successfully.