A path toward a successful solar-driven technology is via construction of durable, efficient, and cost-competitive solar cells, which are capable of effectively exploiting sunlight to produce electricity or fuels. To this end, the fundamental understanding and detailed characterization of heterogeneous photoactive interfaces aimed toward sun harvesting is crucial to boost the device performances. This field is growing and evolving very rapidly and is the subject of increasing research efforts. The challenge stems from the structural complexity of the interfaces and of the related physico-chemical phenomena, whose interlacing determines the overall efficiency of the cells. Indeed, the prerequisites for broad spectral harvesting and favorable energy-level alignment for the intended solar-driven process should be coupled with fast charge separation and collection, competing successfully with photogenerated charge recombination. Efficiency should also come with material and device robustness and stability under demanding operational conditions , particularly in the case of photoelectrosynthetic cells for solar fuel production. To this end, the understanding and the accurate theoretical prediction of surface energetics is crucial to design and employ new material and processes and to rationally optimize photoactive interfaces.Kim et al. explores the electronic structure of different crystalline phases of titania using a newly developed self-consistent optimization approach of hybrid functionals and DFT+U methods, finding that this computationally efficient method delivers predictions on structural and electronic properties of TiO2 phases which are comparable with the experimental and higher level GW results. This methodology is further applied to rutile and anatase interfaces, extremely popular photocatalysts for energy and environmental applications, showing that the solvent medium has a strong influence in band alignment, resulting in almost isoenergetic conduction band minima of these two phases. The transition from the straddling-type to the staggered-type band alignment between rutile and anatase phases could be thus tuned by the choice of the electrolyte medium.The contribution by Boschloo discusses possible ways of improving dye-sensitized solar cells (DSCs), where molecular design of dye sensitizers can lead to endless modifications for optimizing solar performances. Key issues will be the achievement of optimal dye packing on the TiO2 surface to increase light absorption and to achieve a better blocking effect to minimize recombination. Co-sensitization, where two or more different dyes are co-loaded on the semiconductor surface, offers good possibilities in this respect. These dyes shall be coupled to novel redox mediators and hole transporting materials (HTMs) capable to offer much higher output voltage than the traditional triiodide/iodide redox couple. High-performance DSCs are indeed of interest for many applications, ranging from power source for consumer electronics, to building integrated PV and large-scale power generation. The option of high transparency in the near infrared region also opens up for the use of DSC as a top cell in tandem solar cells device.As far as interfacial complexity is concerned, the review article by Boschloo, the research article by Bonomo et al. explores indeed interfacial effects with squaraine dyes, red-infrared absorbing dyes applied to p-type DSCs based on NiO, which could be used to increase photovoltage through coupling with n-type photoanodes. The authors combine experimental design approach and electrochemical impedance spectroscopy (EIS) investigations to optimize the cell performances, finding that NaOH treatment passivates Ni3+ defective sites, avoiding hole trapping and recombination and thus leading to higher current densities and better fill factor. Also in this case the combination of optimal dye packing with surface pre-treatment is exploited for maximized power output.In line with the research lines outlined by Muñoz-Garcia et al. reported the first theoretical study of CuGaO2 delafossite with Mg doping and its adsorption properties toward two anchoring groups as an alternative to NiO for p-type DSCs. The authors were able to show high selectivity with the ab-initio studies toward monodendate and Ga surface binding and further indicating, that despite the p-type metal oxide difficult synthesis, it might deliver higher performance than NiO through higher sensitization.Juang et al. The work demonstrated highly efficient energy harvesting under low light conditions of 200 lux. In focus was the use of cobalt based redox mediators in DSCs with organic sensitizer MK-2, with PCE of 16% surpassing the efficiency of Iodine based electrolytes. The authors pointed out that the results showed the importance to reduce the potential loss for further improvement of DSCs, especially for indoor application.Current strong trend in hybrid solar cells, DSCs and perovskite solar cells toward their application in diffuse light conditions was cemented by the contribution of All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Hip and groin pain often presents a diagnostic and therapeutic challenge. The differential diagnosis is extensive, comprising intra-articular and extra-articular pathology and referred pain from lumbar spine, knee and elsewhere in the pelvis. Various ultrasound-guided techniques have been described in the hip and groin region for diagnostic and therapeutic purposes. Ultrasound has many advantages over other imaging modalities, including portability, lack of ionising radiation and real-time visualisation of soft tissues and neurovascular structures. Many studies have demonstrated the safety, accuracy and efficacy of ultrasound-guided techniques, although there is lack of standardisation regarding the injectates used and long-term benefit remains uncertain. The hip and groin are sites of multiple injuries and inflammatory conditions, including intra-articular and extra-articular pathology, giving rise to an extensive differential diagnosis for hip and groin pain 2. Pain oGiven the complexity of hip and groin anatomy and clinical conditions, imaging-guided injections are useful both for the diagnostic workup and treatment . The maiThis article reviews the commonly performed diagnostic and therapeutic ultrasound-guided injections of the hip and groin region, specifically focusing on the anterior structures including the hip joint, iliopsoas, greater trochanter, pubic symphysis and lateral cutaneous nerve. The anatomy, indication, accuracy and efficacy of these procedures, along with the potential approaches are addressed.For all ultrasound-guided hip and groin procedures, the usual standards for musculoskeletal interventional procedures apply .The choice of ultrasound probe is important – use of a high-frequency (> 10 MHz) linear array transducer is recommended but lower-frequency curvilinear probes may be occasionally required to visualise deep structures in larger patients. A preliminary diagnostic sonographic examination, including colour Doppler of the area to be punctured is necessary to define the relationship of adjacent neurovascular structures. The full description of how to perform ultrasound assessment of the hip and groin region is however beyond the scope of this article .Injections should be performed with adherence to aseptic technique although this varies between institutions and radiologists attributable to resources, training, perceived risk and experience . In a suAfter planning a safe route of access, a line parallel to the long axis of the transducer is drawn on the skin adjacent to the end of transducer where the needle will be introduced. Once the patient’s skin is sterilised and initial needle entry is made adjacent to the mark, the probe can be returned quickly to the same location and orientation by aligning to the skin mark Figure . The neeThe hip joint is a ball-and-socket synovial joint, formed by an articulation between the femur and acetabulum. Intra-articular aetiology of hip pain includes osteoarthritis, inflammatory arthropathy, acetabular labral tears and femoro-acetabular impingement. Injection of short and long acting anaesthetic agents can be useful in confirming hip pathology and differentiating asymptomatic intra-articular pathology from extra-articular conditions that may be the source of symptoms. Complete relief of hip pain following intra-articular injection of local anaesthetic is associated with good surgical outcome following joint replacement .Initial treatment options include activity modification, analgesia and physical therapy. When symptoms persist despite these measures, hip injections can be considered. Intra-articular hip injections can be technically challenging due to depth, variable body habitus, and the proximity to the femoral neurovascular bundle. Image guidance is therefore advocated to ensure safe and accurate needle placement . FluorosTo date, many trials examining efficacy of intra-articular corticosteroid injection for osteoarthritis, either under fluoroscopy 14 or ult15Ultrasound-guided intra-articular hip injections with hyaluronic acid (HA) products  and PRP Two common anterior approaches are typically used both with the patient lying supine. Many prefer the anterior longitudinal approach with the probe aligned along the long axis of the femoral neck. The needle is introduced from an anteroinferior approach and is passed into the anterior joint recess at the femoral head-neck junction Figures  and 2. ADirectly anterior to the hip joint is the iliopsoas muscle-tendon complex with the main tendon inserts on the lesser trochanter. The iliopsoas bursa is the largest bursa around the hip. It is located in between the iliopsoas muscle and hip joint, and may communicate with the hip joint in up to 15% of the population .Disorders of the iliopsoas are a recognised significant source of hip or groin pain. Due to the close proximity of iliopsoas musculotendinous structures and bursa to the hip joint and acetabular rim, they are subjected to mechanical stress typically in the setting of overuse injury, acute trauma, or after total hip arthroplasty secondary to impingement by the prominent anterior rim of acetabular implant or the collar of the femoral prosthesis. Iliopsoas bursal distension is frequently complicated by hip joint pathology including rheumatoid arthritis, osteoarthritis and septic arthritis . Other pThe first-line treatment for iliopsoas disorders are usually conservative, consisting of activity modification, non-steroidal inflammatory drugs, and physical therapy. When conservative therapy fails, an iliopsoas bursal or peritendinous anaesthetic-corticosteroid injection can be considered. Ultrasound has an important role in dynamic assessment of the iliopsoas tendon and guiding a safe method of delivering therapeutic or diagnostic injections. The only potential immediate complication is transient femoral nerve palsy . CompletThe patient is in supine position with the hip in neutral rotation. The transducer is placed transverse to the iliopsoas tendon, parallel to the inguinal ligament and the needle is inserted from a lateral to medial approach. The needle tip is positioned in between the iliopsoas muscle-tendon complex and the ilium at the level of the iliopectineal eminence Figure  or alterThe greater trochanter arises from the lateral junction of the femoral neck and shaft, and has four distinct facets: anterior, lateral, posterior and superoposterior facets. The apex of the greater trochanter is seen between the anterior and lateral facets Figure . The gluGreater trochanteric pain syndrome (GTPS) is a relatively common condition found to affect 10–25% of the general population . GTPS reIn a routine clinical setting, greater trochanteric injections are performed using landmarks without image-guidance. There is strong evidence of a short-term benefit with corticosteroid injection with most patients needing only a single injection, but up to 33% required a second injection and some as many as five injections 40. A speIn contrary to a prior misconception that symptoms were due to bursitis, recent evidence points to tendinopathy as the possible underlying aetiology . JacobsoTrochanteric bursa – The patient is positioned in the lateral decubitus position with the symptomatic hip facing upward and the hips and knees are flexed. The transducer is positioned in the anatomic traverse plane perpendicular to long axis of femur. The needle is introduced using a posterior to anterior approach and is passed into the interface of gluteus medius tendon and the gluteus maximus-iliotibial band Figure  33]..33].The pubic symphysis is an amphiarthrodial joint composed of paired pubic bones with each articular surface covered by hyaline cartilage and separated by an intervening fibrocartilaginous disc with ligaments span the joint. It has limited mobility but stabilises the anterior pelvis during movements with numerous contributing musculotendinous attachments both directly onto its capsule but also onto the skeleton and soft tissues immediately adjacent to it. Of these, the most critical for maintaining the stability are rectus abdominis and adductor longus, which are contiguous and merge with the pubic symphysis capsular tissues in a rectus-abdominis-adductor aponeurosis Figure  45]..45].Athletic pubalgia, sports hernia, sportman’s hernia, Gilmore groin, adductor dysfunction or tendinopathy and osteitis pubis are various terms used to described entities that are either in the same spectrum of disease or share similar mechanism of injury and clinical manifestation. These are common sources of groin pain in athletes, especially those involved in single stance manoeuvres such as soccer, rugby and ice hockey.Initial management of these conditions is usually conservative, including rest, core physical rehabilitation and non-steroidal anti-inflammatory drugs. In patients who fail to respond to conservative therapy, injection into the pubic symphysis or the entheseal soft tissue can be considered. Schilders, et al. 47 report48Pubic symphysis – The patient is in supine position. The symphyseal joint space is initially scanned on the midline pubis in a transverse orientation Figure , the proCapsular/adductor entheseal soft tissue – The patient is in supine position with the leg slightly abducted and externally rotated at the hip. MRI and clinical findings are used for planning the site. The approach is usually lateral and inferior to the scrotum and the needle is advanced directly into the tissues . AnaesthThe LFCN is primarily a sensory nerve and arises from the lumbar plexus, mainly deriving its fibres from L2 to L3 nerve roots. It then runs along the lateral border of psoas major, crosses the iliacus and passes through a fibrous tunnel formed by a small split in the lateral end of the inguinal ligament, medial and inferior to the anterior superior iliac spine (ASIS) Figure . The nerMeralgia paraesthetica (MP) is an entrapment neuropathy of LFCN, resulting in pain, paraesthesia and sensory loss over the anterolateral aspect of the proximal thigh. This is commonly caused by entrapment at the level of inguinal ligament and is usually in association with obesity, pregnancy and ascites . Other cTreatment is usually conservative which includes avoidance of traumatic or external compressive factors, and surgical decompression may be considered in patients who do not respond. Injection of local anaesthetic with corticosteroid at the presumed site of entrapment at the inguinal ligament may offer an alternative to surgery and may also have diagnostic value. The injection of the LFCN is classically described using anatomical landmarks but the failure rates have been reported to be as high as 60% . Ultraso57The patient is in supine position. The lateral end of the probe is placed on the ASIS in an anatomic transverse plane and the medial part of the probe is angled in a caudal direction, so the transducer is parallel with the inguinal ligament. The probe is subsequently moved in a medial-caudal direction to search for LFCN, an oval hyperechoic structure containing several circular hypoechoic fascicles. The needle is inserted in plane from a lateral to medial approach for perineural injection Figure  58]. In. In58]. 57Various ultrasound-guided diagnostic and therapeutic injections can be considered in patients with hip or groin pain. Many studies have demonstrated the safety, accuracy and efficacy of these techniques, although there is lack of standardisation regarding the injectates used and its long-term benefit remains uncertain. Given the advantages of portability, lack of ionising radiation, and visualisation of soft tissue and neurovascular structures, ultrasound-guidance is a highly practical and recommended technique when performing injections in the hip and groin region.


The XXIII Olympic Winter Games were hosted in PyeongChang (South Korea) from the 9th to the 25th of February 2018. The edition included 102 events over 15 disciplines in seven sports. A total of 2,914 athletes from 92 countries competed, including several emerging countries in the winter sports panorama such as Kosovo, Eritrea, Nigeria, and Singapore.An important goal for most athlete-centered research is to be translated into practice, it is used to inform the development of improved athlete preparation and/or performance Coutts, . The resA total of 18 papers have been accepted , written by in total 69 contributing authors from 40 different laboratories (including three winter sports federations) and from 11 countries. Overall, the papers were all directed toward a better understanding of physiological, biomechanical, and training factors related to different Olympic winter sports disciplines: cross-country skiing, alpine skiing, biathlon, Nordic combined, speed skating, snowboarding, and ski-cross.2 . Conversely, lipid metabolism was higher in the leg muscle. These findings can open new perspectives in terms of training regimes applied to the modern cross-country skiing training. However, besides being one of the most physiologically demanding sports, cross-country skiing also involves highly complex biomechanics . An important insight has also been provided by Solli and Sandbakk's case study, which described the training characteristics during pregnancy and postpartum in the world's most successful cross-country skier. Notably, the topic of women competing at the elite level while pregnant is an unquestionable important area of research and there is a paucity of controlled physiological studies  in 2018. The survey items were based on the athletes' typical exercise programs with respect to physical conditioning, ski training, and periodization. Notably, the authors highlighted how the training periodization does not typically follow a traditional annual cycle; rather it is influenced by the availability of good in-snow training conditions. Two distinct characteristics of the alpine skiing training were also highlighted: the importance of strength training (in its different forms) and the careful attention given to training in hypoxic environments. The interaction between hypoxia and strength has been the object of Alhammoud et al.'s study, who explored the effects of acute hypoxia on maximal (as well as explosive) torque and fatigability in the knee extensors of elite alpine skiers. This highlighted the importance of considering explosive strength measurements in the alpine skiing neuromuscular screening tests and prevention programs. The training management between in- and off-snow period is a challenging aspect of alpine skiing  and extrinsic  characteristics  aspects of modern biathlon, highlighting the needs to concurrently optimize physiological and performance capacities of cross-country skiing techniques with shooting.Biathlon combines rifle marksmanship and cross-country skiing while carrying a rifle. It presents similar physiological requirements to those observed for cross-country skiing , Nordic combined athletes presented a lower low intensity volume (~51%) but higher strength and speed training (~39%). In support of this, Rasdal et al. presented the case study of a Nordic combined champion, highlighting his training, and technical and physiological development during the last four seasons preceding the XXIII Olympic Winter Games in PyeongChang (South Korea) in 2018.As described by Rasdal et al. , Nordic Richard and Billaut explored whether or not combining preconditioning strategies could modify muscular oxygenation and improve speed skating performance. Results showed that a preconditioning strategy of combined remote ischemic preconditioning and inspiratory muscle warm-up did not significantly impact the 600-m speed skating performance in elite skaters. This highlights the need for further studies to clearly identify positive strategies to impact speed skating performance, particularly by reducing skeletal muscle deoxygenation.Speed skating is a peculiar sport in which athletes adopt a crouched position and push-off sideward in order to move forward . A distinctive feature of this discipline is that athletes can take advantage of the so-called slipstreaming (or drafting) to catch up with the leading athlete. If slipstreaming is a well-studied strategy in those sports where the preservation of muscle power is a fundamental requirement , then how it affects gravity-powered sports is less investigated. Fuss derived a strategy for slipstreaming in ski-cross by means of a glide model. Results showed that the glide model could be used to test the design of the slope track, precisely identifying the dimensions of the terrain features, and thereby deriving the skiers' speed as well as identifying the critical section of the course.The scientific basis of Olympic winter sports, as well as the studies of how athletes cope with the specific physiological and biomechanical requirements of their discipline, is of paramount importance and interest for exercise physiologists, sport scientists, and particularly coaches. These studies are necessary in order to improve the current understanding of Olympic winter sports performance. The continued evolution of Olympic winter sports is contributing to an enormous accumulation of knowledge, evidence, and relevant training technologies. In this context, the 18 papers that constitute this Research Topic have contributed to our better understanding of the requirements of different Olympic winter sports. The field of study is enormous and touches a considerable number and range of issues. We hope this Research Topic will contribute to the stimulation of further research in all the aspects highlighted within it. The ultimate goal being to improve all Olympic winter sports performances. With the recent implementation by the International Olympic Committee of the Youth Olympic Games, further research is also required to better analyse the practice of winter sports by young athletes at the elite level. Questions about the optimal increase in training load and the specificity of the training content at different age-stages for reducing health and risk of injury are paramount and yet minimally investigated. The next step might come from the “Youth and Winter Sports” congress being held from the 7th to the 8th of January 2020 in Lausanne (Switzerland) prior the next winter Youth Olympic Games, also hosted in Lausanne from the 9th to the 22nd of January 2020.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The spectrophotometric-chemometric analysis of levodopa and carbidopa that are used for Parkinson's disease was analyzed without any prior reservation. Parkinson's drugs in the urine sample of a healthy person (never used drugs in his life) were analyzed at the same time spectrophotometrically. The chemometric methods used were partial least squares regression (PLS) and principal component regression (PCR). PLS and PCR were successfully applied as chemometric determination of levodopa and carbidopa in human urine samples. A concentration set including binary mixtures of levodopa and carbidopa in 15 different combinations was randomly prepared in acetate buffer (pH 3.5).). UV spectrophotometry is a relatively inexpensive, reliable, and less time-consuming method. Minitab program was used for absorbance and concentration values. The normalization values for each active substance were good (r2>0.9997). Additionally, experimental data were validated statistically. The results of the analyses of the results revealed high recoveries and low standard deviations. Hence, the results encouraged us to apply the method to drug analysis. The proposed methods are highly sensitive and precise, and therefore they were implemented for the determination of the active substances in the urine sample of a healthy person in triumph. Levodopa, which has the [(-)-3--L-alanine] chemical expansion, is an antiparkinson drug and a dopamine precursor. It is often used in combination with carbidopa and acts as an amino acid decarboxylase inhibitor . To treaWhen levodopa is combined with carbidopa, the side effects are normally reduced, and the concentration of dopamine is efficacious when these are given at an appropriate level .Multivariate calibration methods (PLS-PCR) were developed using various mathematical operations to determine two or more compounds in the same sample without any chemical separation , 7. The A concentration data matrix (y-block) and absorbance data matrix (x-block) were used to generate PLS and PCR calibration equations at the calibration stage. The first step in the chemometric calculations was a PCA, which allowed the calculation of the amount of available data given the original variables. Using the first few of the prediction variables instead of the components of the prediction variables reduced the number of new components (PC) created. The PLS and PCR were applied, providing precision, accuracy, and selectivity in the results.Different analytical methods have been used in the literature to identify levodopa and carbidopa both separately and together. Moreover, there are several methods for diagnosing Parkinson's disease including spectrophotometric methods –14, elecIn this study, we report analysis of levodopa and carbidopa in urine sample of a healthy person with chemometric methods. Levodopa and carbidopa are contained in the same drug used for treatment of Parkinson's disease. Our aim with this drug was to carry out quantitative analyses using chemometry in urine sample. Levodopa and carbidopa provide the same wavelength and overlapping spectra. Although it is difficult to analyze this situation by classical methods without any preseparation process, the chemometric methods and their determinations were successfully performed next to each other.The validity of this method is clearly examined in terms of accuracy, precision, and selectivity. The chemometric methods used in the study were successfully carried out without any preseparation method for simultaneous determination of levodopa and carbidopa in urine sample of a healthy person. The results were statistically compared to each other and the validity of the methods according to the calculated analytical parameters  was evaluated.Stock solutions of 25 mg/250 mL levodopa (Sigma) and carbidopa (Sigma) in the analytical purity used in this study were prepared in acetate buffer (pH 3.5). Measurement of the synthetic mixture  in the concentration set prepared symmetrically from the active ingredients of the drugs was recorded with the UV-VİS-1700 PharmaSpec Spectrophotometer .−1 and 25.0 mg L−1 of levodopa and carbidopa, respectively, were placed in flasks (25 mL) and dissolved by adding acetate buffer to develop the experimental design. The partial factorial design was used in preparing the calibration set. Chemometric methods are based on suitable experimental design.Absorption spectra of levodopa and carbidopa were recorded at 0.1 ranges from 210 nm to 310 nm. The calibration matrix, training, and validation kits  contain −1) concentrations of levodopa and carbidopa were added to the analysis. In biological samples, matrix effects were taken into consideration and uv-visible measurements were taken. In the calculations of biological samples, the dilution process in the experimental stage was taken into consideration.Twenty-four-hour drug-free human urine samples were collected from healthy individuals and stored at -20°C before analysis. The urine samples were collected over a 4-h period in plastic containers before analysis. A healthy human urine sample was diluted with 20-fold deionized water to remove the matrix. Potentially interfering compounds need to be removed before analysis. Protein precipitation of urine samples was carried out by the addition of acetonitrile. After thawing to ambient temperature, 1 mL of urine was mixed with 9 mL of acetonitrile in order to precipitate proteins from the specimen, vortexed for 3 min. The resulting different , mean, and recovery value (%)  were calThe chemometric methods were validated on the basis of ICH rules –62 for lCiadded is actual concentration, the added concentration of drug; Cifound is predicted concentration, the calculated concentration of drug.In order to verify the validity of the system, one of the calculated parameters is the PRESS (equation ) 63]  64].(2.(264].(2quations  and (4))D values .The limit of detection (LOD) is defined as the lowest concentration of an analyte in a sample that can be detected. The limit of quantification (LOQ) is defined as the lowest concentration of an analyte in a sample that can be determined with acceptable precision and accuracy under the stated operational conditions of the method . F-test [The values obtained from the two chemometric methods (PLS and PCR) used in this study were compared with the variance analysis-Snedecor's F-test . AnalysiThe experimental results of the two methods for human urine samples are given in All statistical parameters and numeric values appear suitable for simultaneous identification of these drugs in human urine samples.With the UV-VIS spectrophotometric method, the drug active ingredients in the healthy human urine sample were determined as fast and reliable. The results obtained from urine samples were compared with the results obtained by conventional UV-VIS spectrophotometry. In this study, the results were obtained with support from chemometric methods and the results were still more reliable. At the same time, due to the fact that each drug substance was determined simultaneously with chemometric methods, time and cost losses were prevented.After certain processes, the proteins were precipitated from the urine, and measurements were taken in the UV-Visible region. The data obtained were evaluated chemometrically. The main advantage of the method is the ability to analyze simultaneously the two compounds under similar conditions. The achieved method validation results show the reliability of the method. The high recovery values also showed that the drugs did not bind to urine proteins. The results obtained suggest that this method could be used suitably for simultaneous determination of levodopa and carbidopa in urine.


Increasing industrialisation, continued population growth and heavy demand and reliance on petrochemical products have led to unprecedented economic growth and development. However, inevitably this dependence on fossil fuels has resulted in serious environmental issues over recent decades. The eco-toxicity and the potential health implications that petroleum hydrocarbons pose for both environmental and human health have led to increased interest in developing environmental biotechnology-based methodologies to detoxify environments impacted by petrogenic compounds. Different approaches have been applied for remediating polluted sites with petroleum derivatives. Bioremediation represents an environmentally sustainable and economical emerging technology for maximizing the metabolism of organic pollutants and minimizing the ecological effects of oil spills. Bioremediation relies on microbial metabolic activities in the presence of optimal ecological factors and necessary nutrients to transform organic pollutants such as petrogenic hydrocarbons. Although, biodegradation often takes longer than traditional remediation methods, the complete degradation of the contaminant is often accomplished. Hydrocarbon biodegradation in soil is determined by a number of environmental and biological factors varying from site to site such as the pH of the soil, temperature, oxygen availability and nutrient content, the growth and survival of hydrocarbon-degrading microbes and bioavailability of pollutants to microbial attack. In this review we have attempted to broaden the perspectives of scientists working in bioremediation. We focus on the most common bioremediation technologies currently used for soil remediation and the mechanisms underlying the degradation of petrogenic hydrocarbons by microorganisms. However, inevitably this dependence on fossil fuels has resulted in serious environmental issues over recent decades. Currently, petroleum production represents a major cause of ecosystem problems. World annual petroleum production is predicted to reach twelve million metric tonnes. British Petroleum Due to this, the effect of petroleum hydrocarbons on the ecosystem, including their eco-toxicity and the potential implications they pose for both environmental and human health is a current area of research focus. In particular soil pollution has been and remains a severe and widespread environmental hazard attracting considerable public and scientific attention. Much of this pollution has resulted from the increased activities associated with petroleum exploration, transport and processing. In addition, the lack of waste oil recycling and the disposal of hazardous oil wastes into landfills without sufficient management has further increased the number of contaminated sites. For instance, during 2005 almost nine oil pollution incidents are reported around the world every day, in addition to an estimation of a yearly oil spill of one million tonnes into the UK terrestrial environment alone There is a clear and urgent need to remediate petroleum hydrocarbon-contaminated areas around the world and several traditional physio-chemical methods such as soil washing, soil vapour extraction, incineration, the use of oil booms and solidification are available for oil spills remediation. Since 2000, remediation strategies based on microbial degradation capabilities (bioremediation) have received extensive attention and have become a current research focus especially in terrestrial environments. Bioremediation is the use of microorganisms, mainly bacteria and fungi, or plants to utilise and break down environmental contaminants such as petroleum into less harmful substances. These techniques have a number of key advantages over traditional technologies including the fact that they are simple to implement, environmentally friendly, applicable over large areas, cost-effective and can lead to the complete destruction of different contaminants 2.From a chemical point of view, the term crude oil is strictly ascribed to a complex mixture of organic compounds comprising predominantly hydrogen and carbon atoms, but also containing smaller quantities of nitrogen, oxygen, sulphur along with traces of metallic constituents 2.1.Aliphatic hydrocarbons represent the major component of crude oil and petroleum products Petroleum contamination in the US is dominated by diesel in which aliphatic hydrocarbons represent up to 90% by volume of the petroleum products 2.2.Aromatic fractions of organic compounds are classified by the presence of two to six aromatic rings (e.g. fused benzene ring) with or without alkyl substituents arranged in linear, cluster or angular configurations within their structure 2.3.The properties of asphaltenes  and resins  have an impact on the behaviour of crude oil during production and refining. They constitute almost 10% of crude oil composition 3.Once petroleum hydrocarbons reach an environment, primary biological damage occurs by blocking the supply of water, nutrients, oxygen and light, affecting soil fertility, plant growth and germination 4.Considering the nature and extent of hydrocarbon pollution in soils and in order to predict how successful oil remediation approaches will be, understanding the fate and behaviour of such contaminants in the environment is vital. During an oil spill, weathering occurs and the oil is subjected to a variety of physicochemical processes The biodegradable fraction of organic pollutants in soils is the fraction that is easily desorbed to or from the soil particles and exist in the aqueous phase. It is well established that as the interaction between soil particles and pollutants increase, there will be a proportional reduction in contaminant extraction and biodegradation 5.Microorganisms have the ability to metabolize many organic contaminants, using them as an energy source or converting them to non-toxic products . Different microbial electron acceptors such as oxygen, nitrate, manganese, iron and sulphate can be involved in the biotransformation of aliphatic and aromatic hydrocarbons. Microorganisms can activate and oxidize hydrocarbon compounds. The addition of one or two hydroxyl groups to the hydrocarbon skeleton represents the first step in the aerobic catabolism of hydrocarbons. During hydrocarbon degradation, activation is achieved through different enzymes, for example by the introduction of molecular oxygen to the substrate , the addition of two hydroxyl groups  or the addition of one atom of oxygen into the hydrocarbon  5.1.Microbial degradation of petroleum hydrocarbon compounds is carried out by a range of microbial groups capable of degrading a wide range of target constituents present in oil contaminated environments. A biodegradation pathway is a gradual transformation of organic contaminants into intermediates of the central intermediary metabolism. For example, in the case of aliphatic hydrocarbons , microorganisms utilise soluble or integral-membrane non-haem iron monooxygenases; these enzymes, alkane hydroxylases (e.g. AlkB) hydroxylate the substrate 5.2.Pseudomonas, Rhodococcus, Sphingobium and Sphingomonas spp. are ubiquitous in the ecosystem. These microbes are capable of degrading aromatic hydrocarbons; the catabolism process commences with an oxidation step of one of the aromatic rings and the structured fracture of the substrate to PAH metabolites and CO2. Fundamentally, the reaction is catalyzed by aromatic hydrocarbon ring hydroxylating enzymes (ARHDs) and form cis-dihydrodiols. The dihydrodiols are then oxidized via a dehydrogenase reaction to produce PAH dihydroxy derivatives which are further exposed to the action of ring cleaving dioxygenases. The action of aromatic ring cleavage is accompanied by integration of a pair of oxygen atoms into the dihydroxy derivative molecule. Dihydroxylated intermediates may then be cleaved through either an intradiol manner (ortho) cleavage pathway, or through the intradiol ring (meta) cleavage pathway, with the formation of catechols and subsequently metabolised to carbon dioxide and water through the TCA (tricarboxylic acid cycle) cycle Hydrocarbon-degrading microorganisms such as Pleurotus ostreatus and Phanerochaete chrysosporium) Since lignin contains a selection of aromatic compounds, these enzymes participate in the oxidation of lignin as well as different organic complexes 6.Mycobacterium spp., Arthrobacter spp., Marinobacter spp., Achromobacter spp., Alcaligenes spp., Corynebacterium spp., Flavobacter spp., Micrococcus spp., Nocardia spp. and Pseudomonas spp., Bacillus, Dietzia, Gordonia, Halomonas, Cellulomonas, Rhodococcus and halotolerant Alcanivorax spp. Aspergillus spp., Penicillium spp., Cunninghamella spp., Fusarium spp., Saccharomyces spp., Amorphoteca spp., Syncephalastrum spp., Neosartorya spp., Phanerochaete spp., Paecilomyces spp., Talaromyces spp. and Graphium spp. are capable of mineralizing petroleum hydrocarbons with varying degradation rates Cunninghamella elegans, a filamentous non-ligninolytic fungus was isolated from soil and has been implicated in the transformation and degradation of several PAH compounds including benzo[a]pyrene, 9,10-dihydrobenzo[a]pyrene and benz[a]anthracene Psilocybe spp., Cyclothyrium spp. and Penicillium simplicissimum are additional examples of filamentous fungi which have been reported to exhibit hydrocarbonoclastic activities against different PAHs Hydrocarbonoclastic microorganisms are the main agents of the degradation of petroleum hydrocarbons, owing to their associated metabolic capabilities . Reviews7.Since there are many soil dwelling microbes that are capable of breaking down the diverse fractions of hydrocarbons and which survive under different conditions, each site may necessitate a specified bioremediation treatment. The different generic methods and strategies of bioremediation technologies being applied currently are natural attenuation, bioaugmentation, biostimulation and phytoremediation. The techniques are summarized in 7.1.By definition, natural attenuation is the simplest bioremediation process by which the indigenous microbial population (bacteria and fungi) eliminate or detoxify petroleum and other hydrocarbon pollutants hazardous to human health and/or the environment into less toxic forms in order to attenuate the polluted site. During this process the indigenous microbes utilise hydrocarbons as the sole carbon source based on their natural, metabolic pathways. This technology requires simply monitoring the process. When site pollution occurs, indigenous hydrocarbon-degrading microorganisms will increase rapidly and adapt to the freshly added pollutants resulting in contaminant degradation; however microbial diversity may be reduced 7.2.in situ bioremediation methods is bioaugmentation. This application involves the addition of single strains or consortia of hydrocarbon-degrading microbes (bacteria or to a lesser extent fungi) with catalytic capabilities to remediate contaminated sites in order to accelerate the biodegradation of undesired organic compounds. The bioaugmented hydrocarbon utilizers are normally isolated from petroleum hydrocarbon polluted environments The capacity of the microbial community in the soil to metabolize petroleum pollutants is determined by their structure and diversity 7.3.2) and represents an effective technology for restoring oil polluted and nutrient deficient sites A widely practiced bioremediation technology that exploits the capability of microbes to degrade and/or detoxify petroleum pollutants in the soil is termed biostimulation. This procedure results in the stimulation of the growth and activity of the indigenous microorganisms present in the contaminated site through the addition of nutrients in order to accelerate the rate of natural biodegradation 8.The key purpose of remediating polluted sites is to diminish the hazard of contaminants to human health as well as the environment through the application of optimal remediation techniques Limited bioavailability of hydrocarbons to microorganisms can result in a less effective bioremediation process by limiting the rate of hydrocarbon degradation. The interaction between hydrocarbon degrading microbes, soil matrix and the contaminants plays an important role in the bioremediation process. Soil organic matter is one of the most significant factors having a dominating influence on the interactions between soil and the organic pollutant The degradation rate of petroleum pollutants is generally higher during the early stage when the pollutants are easily bioavailable; in contrast in the second remediation stage contaminant bioavailability is limited as a result of hydrocarbons being sequestered. Generally once this stage has been reached no further degradation occurs during the rest of remediation Like soil organic matter, ageing of the polluted soil can also adversely affect the degradation of petroleum hydrocarbons. A number of studies have reported greater rates of hydrocarbon degradation in freshly polluted soils compared with aged hydrocarbon fractions. This may result from the contaminant being partitioned into the soil organic matter fraction or penetration into small pores leading to a decline in pollutant bioavailability to microbes The main factors and their impact on the feasibility and rate of petrogenic hydrocarbon biodegradation in soil are summarised in 9.The widespread utilisation of petroleum hydrocarbons in different industrial applications presents a challenge for the remediation of polluted sites. In most cases, the ability of these contaminants to sorb onto mineral and organic matter of the soil determines the efficiency of the remediation process. A significant amount of bench-scale work has concentrated on the ability of a diversity of microbes including bacteria and fungi to transform these complex compounds. The pathways of aerobic and anaerobic degradation of petrogenic hydrocarbons have been established and this has led to an interest in the potential use of microbes to degrade petroleum-contaminated sites. To date, bioremediation approaches have shown significant promise. However, further research to overcome several implementation issues is required. In addition, more field and pilot scale trials are important to evaluate the efficiency of these processes, taking into consideration that each site is different and numerous factors must be considered. An effective remediation of a contaminated site depends on the appropriate selection and design of the remediation technique.


The amount of circulating drug in the bloodstream of the volunteers will be measured using liquid chromatography combined with mass spectrometry. Pharmacokinetic obtained parameters will be maximal plasma concentration, minimal plasma concentration, predose concentration, 24 hour post predose concentration, the time for maximum concentration. The area under the curve will be determined by the trapezoidal rule. Male Versus female data will be compared using 2-tailed t-test. RESULTS/ANTICIPATED RESULTS: We anticipate that: (1) Hispanic/Latino women will have longer circulating times of the drug in the bloodstream and higher maximum concentrations, compared with men. (2) Hispanic/Latino men and women will have higher amounts of the circulating drug, compared with already reported pharmacokinetic data of non-Hispanic Caucasian men. DISCUSSION/SIGNIFICANCE OF IMPACT: Gender differences have been elucidated in the prevalence rates of substance abuse, health service utilization, treatment outcomes, and physiological consequences of drug consumption in the United States. It is known that in general, women progress from drug use to dependence must faster than men; women also suffer more severe physical and emotional consequences than men, yet women seek treatment for drug addiction in lower rates compared with men. Women also show lower pharmacological treatment effectiveness as they are less likely to feel satisfied upon entering a substance abuse treatment and they show higher cravings. Sublingual buprenorphine is a very popular and relatively new medication used primarily for opiate addiction since 2002. Gender differences have been elucidated in the pharmacology of buprenorphine sublingual tablets used for the treatment of opioid addiction. One study showed that women had higher concentrations of circulating parent drug and it is metabolites compared with men. One metabolite in particular norbuprenorphine was found in almost double the plasma concentration in women. Interestingly, gender differences were not pursued at all by the Pharmaceutical Company sponsoring the approval of the sublingual Buprenorphine by the FDA. The cytochrome enzyme CYP 3A4 responsible for the metabolism of Buprenorphine has higher activity in Caucasian/African American women compared with men. However these studies failed to design and recruit significant amount of patients with Hispanic ethnicity to adequately elucidate the gender differences within this ethnic group. Higher plasma concentrations and longer circulation times of a drug may result not only in lower efficacy outcomes but also higher toxicity and undesired effects. Unfortunately, the lack of pharmacological effectiveness and lack of satisfaction in women undergoing drug treatment programs has not been adequately studied to understand the gender difference in pharmacological treatment outcomes between Hispanic/Latino men and women. Due to the under-representation of Hispanic/Latino men but most importantly women in s studying the pharmacology of sublingual Buprenorphine, and considering the well-established gender difference of the principal enzyme (CYP 3A4) responsible for the pharmacology of Buprenorphine, we are proposing a pilot study of the pharmacology of sublingual Buprenorphine in Hispanic/Latino volunteers living in Puerto Rico with equal number of male and female patients. We expect our research to clinically and scientifically elucidate the gender differences of sublingual buprenorphine for opioid addiction in Hispanics/Latinos. The outcome of such research will be the foundation of subsequent clinical studies that aim in updating the current standard of care for Hispanic/Latino men and women that require therapy for opioid addiction.OBJECTIVES/SPECIFIC AIMS: The objective of this study is the pharmacology of sublingual Buprenorphine in Hispanics/Latino men and women. Specifically we plan to: (1) Administer sublingual buprenorphine to Hispanic/Latino men and women volunteers, and measure the circulating amounts of the drug in the bloodstream as a function of time; that is, pharmacokinetics of buprenorphine. The goal of the proposed study is to evidence that there are gender and ethnic differences in the pharmacokinetics of sublingual buprenorphine between not only Hispanics/Latinos and non-Hispanics/Latinos (Caucasian), but also within Hispanic/Latino men and women. METHODS/STUDY POPULATION: We are proposing a phase 1 of buprenorphine using 12 healthy volunteers. To test for differences in pharmacokinetics between Hispanic/Latino men and women, 6 Hispanic/Latino men, and 6 Hispanic/Latino women 21 years of age and older will be recruited. The volunteers should be living in Puerto Rico, and must have both parents born in Puerto Rico. Sublingual buprenorphine will be administered using a low dose of 16 mg one time only. Blood samples will be collected from each volunteer at


Understanding the composite damage formation process and its impact on mechanical properties is a key step towards further improvement of material and higher use. For its accelerated application, furthermore, practice-related modeling strategies are to be established. In this collaborative study, the damage behavior of carbon fiber-reinforced composites under cyclic loading with load reversals is analyzed experimentally and numerically. The differences of crack density evolution during constant amplitude and tension-compression block-loading is characterized with the help of fatigue tests on cross-ply laminates. For clarifying the evolving stress-strain behavior of the matrix during static and fatigue long-term loading, creep, and fatigue experiments with subsequent fracture tests on neat resin samples are applied. The local stress redistribution in the composite material is later evaluated numerically using composite representative volume element (RVE) and matrix models under consideration of viscoelasticity. The experimental and numerical work reveals the strong influence of residual stresses and the range of cyclic tension stresses to the damage behavior. On the microscopic level, stress redistribution dependent on the mean stress takes place and a tendency of the matrix towards embrittlement was found. Therefore, it is mandatory to consider stress amplitude and means stress as inseparable load characteristic for fatigue assessment, which additionally is influenced by production-related and time-dependent residual stresses. The phenomenological findings are incorporated to a numerical simulation framework on the layer level to provide an improved engineering tool for designing composite structures. During mechanical loading of fiber-reinforced plastics (FRP), damage phenomena occur with increasing stress levels and duration, which can lead to material degradation. The damage is determined by the inhomogeneity of the material across different scales, which is characterized microscopically by the characteristic lengths of filament and matrix, mesoscopically by the thickness of the diverse oriented layers, and macroscopically by the spatial laminate expansion. Analogous to this geometrically motivated scale definition, the damage phenomena can be classified into micro, meso, and macro damage. On the macroscopic scale, composite material damage can be observed as stiffness and strength degradation through the formation of damage on the meso, or layer, level. The damage phenomena, such as delamination, fiber-breaking and matrix cracks, are formed statistically distributed in the laminate and are initiated by microscopic phenomena in the matrix and fiber-matrix interphase. The characteristic of damage caused by cyclic loading is determined mainly by mean stress and stress amplitude and thus by sign and orientation of the varying load vector with respect to the fiber direction. Additional factors influencing the crack initiation and growth are the load frequency and load sequence, environmental conditions , manufacturing process, and material configuration.Recently an increasing attention is paid on understanding load reversals and their detrimental effect on damage accumulation ,3,4,5,6.Gamstedt et al.  studied Quaresimin et al.  analyzedThese findings are supported by results for carbon fiber-reinforced (CFRP) cross-ply laminates tested at four different load ratios published by the authors of this publication in earlier work ,7. The fHowever, the possible reasons of the accelerated damage growth under reversed loading are still an open research topic and the driving mechanisms on the microscale have to be analyzed to derive physical-based macroscopic formulations of the damage growth.Over the last few years, a great effort has been devoted not only to experimental investigations of fatigue damage of composites but also to the development of numerical fatigue damage models . DependiIn ,18 a fatIn extension of this scientific work, the damage phenomenology regarding fatigue loads with load reversals on different length scales is investigated and mathematically described in this collaborative study. The mesoscopic damage initiation and progression in cross-ply laminates is analyzed for describing the material degradation during fatigue and micromechanical explanations for the observed behavior are worked out using neat resin experiments and representative volume element (RVE) simulations for constant and fatigue loading.The main objectives of this paper are: (1) The experimental investigation of the damage phenomenology under cyclic loading with load reversal on different observation scales, (2) the analysis and description of micromechanical damage by means of microscale experiments and finite element modeling using an RVE, (3) linkage of the micromechanical findings with the mesoscale damage evolution and elaboration of the influence of constant amplitude and block loadings and (4) the development of numerical methods to consider the effects of load reversals and load sequence on fatigue damage evolution.The present research therefore analyses the fatigue behavior of CFRP at the meso and micro scale in order to elaborate the driving mechanisms of damage initiation and growth under different load ratios in The specimens used within this study were manufactured from a T700SC carbon fiber and an Araldite LY556 epoxy resin system. The unidirectional  were tested. Using these results a connection between the observed microscopic effects and the detected macroscopic crack density variation shall be established.The samples were loaded in tension-tension fatigue  to exemplary investigate the behavior of the epoxy resin in the transversely loaded plies. The observed residual stress after manufacturing and static loads were simulated by tensile-creep loading. Three loading durations were chosen between 1800 s and 7200 s applying a mean static stress of 43 MPa and a temperature of 50The ultimate tensile strength increases for both test configurations in comparison to the reference sample, where an average ultimate tensile strength of 74.5 MPa has been measured. The effect of increasing strength during the tensile test can be consistently observed with increasing load duration for fatigue, as well as, creep loading. While the creep loading shows an increase of up to 11% (83.1 MPa) the fatigue samples show a lower strength gain of 2.3%  algorithm from Yang et al. [For the 90g et al.  was impli-th direction, l is the length of the model in i-th direction. This boundary condition ensures the periodicity of the modeled section for representing the entire UD-layer under loading [For the fiber region, coupled temperature-displacement elements with reduced time integration (C3D8RT) were used and for the matrix, coupled temperature-displacement elements (C3D8T) were used. To ensure a periodic deformation of opposite boundaries and zero averaged stress gradients over the model, the following boundary conditions were defined for the nodes on model boundaries: loading .The material behavior of the fibers was assumed to be transversal isotropic and linear elastic. The transverse elastic properties of the T700SC fibers were assumed to be similar to T300 fiber and the values were taken from .K is constant. The time dependence is only determined by the deviatoric component. The viscoelasticity is described by a generalized Maxwell-model with a mathematical formulation of Prony series, Equation  strength and stiffness degradation factors . This shell element is defined as a The numerical simulations are performed under force-controlled loading. Furthermore, a block-wise analysis of the load cycles is carried out employing a cycle-jump technique to avoid the numerically inefficient cycle-by-cycle analysis. This block-loading strategy results from the applied energy approach according to Pfanner . A detaiined cf. .As shown in ysis see .In the first part of this study, the effects of load reversals on the damage evolution at different stress ratios are investigated under constant amplitude loading (CA). Therefore, the following global stress ratios are selected: n. Therefore, the degraded laminate module The calculation results for the various stress ratios under CA loading are depicted and compared in Equation .(9)Ex,dThe simulations are carried out with a block length of  in Just , a good In the second part of this study, the influence of load reversals at block-loading is investigated. ding cf. .When comparing short with long load blocks, the FDM calculates a marginally higher damage for short load blocks. This effect is visible in both TC and CT sequences. The deviation of the damage state in both cases  is less than one percent after A similar trend of damage evolution can be observed by comparing the obtained simulation results with the crack density evolution observations from The present collaborative study provides experimental results on the damaging process of CFRP cross-ply laminates under constant amplitude and block-loading conditions, mathematical methods for describing the mesoscopic degradation as well as the mesoscopic damage behavior and micromechanical explanations for the observed behavior based on neat resin experiments and RVE simulations for constant and fatigue loading.The results for block-loading experiments for TC and CT sequences, respectively, did not show significant differences in terms of crack formation and delamination growth. However, compared to fully reversed constant amplitude tests with the same stress levels, the block-loading experiments showed lower crack densities and less delamination growth. Accompanied resin creep and fatigue experiments in tension revealed a tendency for increasing stiffness and strength of the matrix over time with the potential of influencing the damage behavior at different stress ratios.Simulation with micromechanical RVE-model showed similar strain distribution in matrix when the FRP is loaded in different sequences with the same stress levels and therefore support the experimental findings. It was consistently found that only by considering residual stresses the mesoscopic damage behavior at different stress ratios can be interpreted. It has been shown additionally that residual stresses change significantly over time. Furthermore, the differences in the cracking behavior are also attributed to the range of the strain energy release rate for different load ratios considering residual stresses. By calculating the damage-driving range of ERR with respect to the changing residual stresses, the authors were able to pool the different sets of experiments into one Paris-like crack growth relation.The experimental findings are further on incorporated to the energy-based FDM. The user-defined material subroutine, proposed for fatigue damage analysis on meso- and macro-scale levels, was extended for the analysis of variable amplitude loading and the consideration of manufacturing-induced residual stresses. It was successfully shown that load sequence effects in the context of load reversals can be reproduced with the flexible modeling approach. As seen from the experiments, the various TC load sequences examined showed a very similar damage evolution. In comparison to a constant TC alternating load, the prediction with load sequences results in a significantly accelerated increase in damage.


The present report describes one of the rarest complications of cesarean section, uterocutaneous fistula, diagnosed on magnetic resonance imaging (MRI). A 37-year-old female with history of lower segment caesarean section (LSCS) four years previously presented with a chief symptom of discharge from the right end of a Pfannenstiel incision and on further evaluation was found to have uterocutaneous fistula arising from the LSCS scar to the right end of the abdominal incision. Uterocutaneous fistula is a rare delayed complication of LSCS and MRI plays a definitive role in the accurate diagnosis and delineation of the tract. The present case highlights that although rare, uterocutaneous fistulae must be kept in mind in patients presenting with discharge from the abdominal incision site and MRI evaluation should be performed in such cases for appropriate delineation of the tract. PRECIS: To identify the possible risk factors for postpartum urinary retention.. Uterocutaneous fistulae, being a rare condition, need appropriate diagnosis for which magnetic resonance imaging (MRI) plays the most important role, thereby helping in the proper delineation of the tract to guide the appropriate management. The most common cause of uterocutaneous fistula is incomplete closure of the cesarean section wound. Earlier diagnosis can be made using fluoroscopic or cross-sectional modalities. Surgical repair is the treatment of choice with preoperative gonadotropin administration showing better outcomes, but few cases may result in hysterectomy. We describe this case of uterocutaneous fistula, which occurred 4 years after a caesarean section and was diagnosed using MRI.Uterine fistulae usually occur between the uterus and bowel or bladder  with uterocutaneous forming the rarest variety of uterine fistulae. The fistulae occur due to postoperative injuries or infections, use of drains, and incomplete closure of incisionA 37-year old female with a history of lower segment cesarian section (LSCS) performed four years previously presented with the chief symptom of discharge from the incision site. MRI of the pelvis was performed, which revealed an enhancing fistulous tract originating from the site of the lower segment of the cesarean section and traversing through the parietal wall opening at the right edge of abdominal incision scar . The dia,5.During the era of classic cesarean section, a number of cases of uterocutaneous fistula were reported but with the advent of LSCS, the frequency has decreased to a large extent. Most uterocutaneous fistulae owe their origin to infections  complicating uterine or abdominal scars. Besides LSCS, the causes of uterocutaneous fistulae include post septic abortion, placement of drain, missed uterine perforation following a diagnostic laparoscopy,7. Other rare causes that may result in the formation of uterocutaneous fistula are patients with multiple abdominal myomectomies, history of hysterectomy, and as a primary presentation in underlying gynecologic malignancy such as endometrioid adenocarcinoma, which can predispose the weak cesarean scar to fistula formation,7,8. The blood leakage from the incision site during menstruation has been described as pathognomonic of the uterocutaneous fistula.Cases of post-partum hemorrhage wherein B-lynch sutures are placed have high risk of scar dehiscence, which may result in uterocutaneous fistula,3. CT imaging helps in the proper delineation of the tract after the injection of the contrast agent through the abdominal site, but soft tissue resolution of CT scans is less compared with MRI,11. MRI provides good soft tissue resolution, avoids radiation , and helps in proper delineation of the fistulous tract and its relation to the surrounding viscera. The assessment of other pelvic organs with greater spatial resolution is possible. Intravenous contrast administration shows the enhancement of the granulation tissue along the fistulous tract, which gives a clue about the active status of the fistula. Further, contrast agent can also be administered via the abdominal site as in other investigations to check the patency of the.The various modalities that can be used in the diagnosis of uterocutaneous fistula include fistulography with injection of contrast through the skin site, hysterosalpingography with injection of contrast via cervix, computed tomography (CT) scanning, and MRI. Fistulography and hysterosalpingography define the fistulous tract but cannot provide details of its communication with the other intra-abdominal visceraHence, MRI forms the best investigative modality in the assessment of uterocutaneous fistulae and other pelvic post-operative complications.


Past research has demonstrated an association between health and cognitive resources, intrinsic motivation, and activity participation in older adulthood, both cross-sectionally and from a daily perspective . This highlights the potential importance of motivation as a mediator of the impact of changing personal resources on engagement in cognitively beneficial activities. This study expanded on prior research by examining these relationships longitudinally in a large representative sample of adults over 50. Specifically, we used data from the Health and Retirement Survey (N = 5600) to create two 4-year longitudinal assessments, with multi-level structural equation modeling used to test the mediating role of motivation on everyday activity engagement. Consistent with expectations from Selective Engagement Theory , motivation served as a partial mediator of the impact of changing resources on engagement, with the effect being selective based on the cognitive demands of the activity.


The benefits of technology to alert family caregivers to the needs of persons with Alzheimer’s disease or related dementias (ADRD) are unclear. Previous research indicates that remote activity monitoring (RAM) system alerts can be alternately reassuring and highly stressful for caregivers. We conducted a parallel convergent mixed-methods analysis of 62 primary caregivers of persons with ADRD to evaluate the association between the number of alerts and caregiver outcomes after 6 months. We assessed caregiver-reported usability of the system as well as self-efficacy, sense of competence, and distress as primary outcomes. Linear regression models tested the association between the number of alerts and caregiver-reported usability and primary outcomes. The number of alerts declined over the first 6 months of system use and was not associated with a change in system usability or primary outcomes. Thematic analysis of caregiver-reported perceptions of RAM use simultaneously probed for more in-depth understanding of caregiver experiences of and feelings towards RAM. Preliminary analyses reveal that 28% of caregivers comments were positive, noting benefits such as early warning of health concerns and peace of mind. 34% of comments were neutral or mixed, and 38% were negative. Concerns included false alarms and accidental triggers, losing sleep due to alarms, and difficulties using the system. These findings help characterize the adjustment period to use RAM technology. The mixed-method results inform future research studies and applications of RAM systems so that researchers and caregivers can better understand the initial adjustment period, address concerns, and avoid discontinuing RAM use prematurely.


Objective: We aimed to investigate the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (mGCC) thickness in patients with chronic phase of nonarteritic anterior ischemic optic neuropathy (crNAION) analyzed by spectral domain optical coherence tomography (SD-OCT).Methods: Patients with crNAION, and healthy control subjects were enrolled in the study. All participants underwent SD-OCT for measurement of pRNFL, mGCC, and central macular thickness (CMT). The measurements of the eyes of the patients with crNAION were compared with those of the control subjects and unaffected fellow eyes.Results: A total of 25 patients with crNAION were eligible for the study. The control group consisted of 50 healthy subjects. The pRNFL and mGCC thickness in eyes with crNAION were found to be significantly thinner in all quadrants when compared to those of healthy control subjects and unaffected fellow eyes. The CMT of the eyes with crNAION was similar to that of the healthy control subjects.Conclusions: We demonstrated that mGCC and pRNFL thickness measurement by SD-OCT are capable of detecting axonal damage in eyes with crNAION. Furthermore, this study used SD-OCT and found that mGCC and pRNFL had the ability to detect GC loss in the eyes of the patients with crNAION. It is the second most common optic neuropathy after glaucoma, with a recently estimated incidence of 82 cases per 100,000, of which the population is over 67 years old [4].Nonarteritic anterior ischemic optic neuropathy (NAION) is a common vascular disease in elderly patients presenting with unilateral, painless, sudden vision loss with optic disc edema [5]. The RGCs comprise three layers in the retina: the mRNFL (macular GC axons), the GC layer (GC bodies), and the IPL (GC dendrites). All three layers are defined as the GCC [6]. Nonarteritic anterior ischemic optic neuropathy is caused by acute ischemic damage of the anterior region of the optic nerve due to reduced perfusion of short posterior ciliary arteries and afterwards it leads to apoptosis of retinal ganglion cells (RGCs) and optic nerve atrophy [7] demonstrated that RGC axons showed severe degenerative changes within 1 week after the acute ischemic event. The pRNFL thickness was significantly increased by disc swelling that may mask retinal ganglion cell loss in the acute stage of disease. The GCIPL thickness is less likely to be affected by optic disc edema in the acute phase of NAION compared to RNFL. Moreover, GCIPL might be useful for the detection of the axonal loss over time with OCT.In an experimental AION model, Lee et al. [8]. One might be able to indirectly document the loss of RGC by measuring the macular ganglion cell complex (mGCC) and the peri-papillary retinal nerve fiber layer (pRNFL), since the aforementioned provide quantitative outcomes [6].In the chronic phase of NAION (crNAION), degeneration of RGCs is usually observed after the acute phase. The pallor of the optic disc is a subjective method to evaluate the loss of ganglion cells and their axons. Histological studies of the eyes with NAION have demonstrated significant damage in the optic nerve axons [9]. The majority of the imaging and SD-OCT studies conducted on NAION aimed to analyze the optic disc and peri-papillary retina, however few studies have focused on macular structure .Spectral domain optical coherence tomography (SD-OCT) imaging is a useful device used in neuro-ophthalmological diseases [12], the thinning of the GC and inner plexiform layer (IPL) and the pRNFL [6]. Moreover, a correlation between GC+IPL thickness and the contralateral hemispheric loss of VF was reported in NAION [13].The measurement of the macular structure may provide more useful information in neuro-ophthalmological diseases, such as glaucoma, and NAION, since the axons of the RGC are directly involved in the optic nerve pathology and their preservation is important to the prevention of the vision loss. Previously, it has been reported that macular thickness is correlated with visual field (VF) loss . The inner and outer rings were divided into four quadrants: superior, nasal, inferior, and temporal. The mGCC thickness was measured in nine ETDRS subfields . OCT measurement of the eyes of the patients with crNAION was compared to those of the control subjects and unaffected fellow eyes.We obtained SD-OCT  measurements for each eye. Furthermore, all the subjects underwent the same acquisition protocol, including a peri-papillary scan with 3.5 mm diameter circle scans with automatic real time (ART) of 90 and a macular raster scan centered on the fovea . Retinal layer segmentation was performed automatically using the Spectralis OCT. Then, we quantified the thickness of the following layers: (1) pRNFL , (2) mGCC; GC layer + IPL + macular RNFL (mRNFL), and central macular thickness (CMT). For the study, the measurements including macular structure thicknesses were automatically calculated in the 9 ETDRS areas  . Since the RGCs die as a result of diseases such as NAION, the GCC becomes thinner. Since these layers are directly influenced by GC loss, the GCC scan might be useful in detecting this loss.RGCs comprise three layers in the retina: the mRNFL (GC axons), the GC layer (GC bodies), and the IPL (GC dendrites). All three layers are defined as the GCC . It appears that ischemic injury to the axons results in secondary metabolic damage to RGCs culminating in their death. These histopathological changes are difficult to document in vivo. On the other hand, one might be able to indirectly document the loss of RGCs by the measurement of mGCC and the pRNFL, since these ensure quantitative outcomes [17–19].Histopathology of NAION involves ischemic edema, cavernous degeneration and atrophy of the axons in the optic nerve as well as apoptosis of RGCs [20]. Segmentation of macular OCT scans enables the in vivo quantification of the integrity of retinal neuronal layers. Furthermore, it analyzes the neuronal integrity since it can demonstrate the thinning of mGCC and pRNFL in chronic optic nerve damage, particularly in NAION .Macular parameters obtained by SD-OCT have been investigated in other non-glaucomatous optic neuropathies [23] observed that the pRNFL thickness (particularly the superior RNFL thickness) in NAION eyes was increased in the acute phase, becoming thinner thereafter and reaching its lowest level after the 6th month. It has been reported that crNAION causes a decrease in pRNFL thickness . In our study, the pRNFL thickness was decreased in all quadrants of the eyes with crNAION. Our findings were in accordance with literature.Contreras et al. . Our study results demonstrated that the group of patients with crNAION had significantly thinner mGCC thicknesses than the unaffected fellow eye and the control group. We found that the mGCC losses in patients with crNAION were in accordance with literature .In addition, the association between crNAION and mGCC loss was reported in literature [25].However, it is important to remember that changes in OCT layer thickness do not correspond to pathological specificity and that changes may not even occur directly in the layer under study [In the present study, a second control group was generated from the unaffected fellow eyes of the NAION patients to eliminate possible confusing factors such as vascular disorders. On the other hand, a relatively small sample size of the study groups was a limitation of this study. The lack of electrophysiological tests or correlation of the visual field with the SD-OCT findings was another limitation. Only Turkish subjects were included in this study, and there may be differences among various ethnicities. Further investigations with a larger sample size including various ethnicities are required to validate our findings.We demonstrated that mGCC thickness measured by SD-OCT is capable of detecting axonal damage in crNAION eyes. This study used the SD-OCT and found that mGCC and pRNFL have the ability to detect GC loss in the eyes of patients with crNAION.Conflict of InterestNone AcknowledgmentsThe authors have no financial interest in any of the products mentioned in the paper. We are grateful to Dicle University DUBAP for their sponsorship regarding the English editing of this paper.


Cable-bolt failures due to stress corrosion cracking (SCC) could significantly compromise the sustainability and long-term stability of underground constructions. To fully understand the SCC of cable bolts, a two-step methodology was implemented: (i) long-term cable-bolt coupon tests using mineralogical materials collected from underground mines; and (ii) accelerated full-scale cable-bolt tests using an acidified solution. In the long-term tests, a novel three-point bending coupon was designed. The effects of mineralogical materials on SCC were evaluated under the simulated underground bolting conditions through the application of “corrosion cells”. For accelerated tests, SCC resistance of different type of cable bolts was examined using the new designed tensile-loading apparatus under the periodically increasing strain-rate loading mechanism. It was identified that mineralogical materials and applied stress intensity accelerated the corrosion process of the cable bolts. The number of wires and wire surface conditions in different types of cable bolt directly affected SCC susceptibility. The cable bolts with a greater number of wires provided higher resistance to SCC. The developed experimental methodologies can be applied to study SCC in other reinforcement materials and the results can be used to design optimal support systems in different environmental and geotechnical conditions. In mining and civil engineering, the construction of the underground excavations such as roadways and tunnels disturbs the original stabilization of the rock mass. The stresses around the excavations redistribute both vertically and horizontally which can cause the fracture and collapse of the strata, potentially leading to the injury of the human and loss of equipment ,2. To reIn the past few decades, with the ubiquitous application of cable bolts at great mine depths, an increase in the frequency of cable bolts failures in reinforcement systems was observed. One of the causes of such failures was identified to be stress corrosion cracking (SCC). SCC is defined as the degradation process of material through the initiation and propagation of cracks under constant loads while exposed to corrosive environments ,13,14,15In underground reinforcement systems, SCC could induce the catastrophic failure of cable bolts, potentially leading to falls of ground. Generally, cable bolts are installed in predrilled boreholes using grout or cement, anchoring the weak layers to stable rock strata through the load-transfer capacity between bolt-anchor and grout interface. SCC failures of cable bolt were observed to occur in different geological and hydrological conditions. The SCC related rock bolt and cable-bolt failures in underground reinforcement system were first observed in the 1990s in the United Kingdom where the collapse of a roadway roof occurred ,23. SCC Maintaining integrity of the installed cable bolts during their service time is crucial for the sustainability and long-term stability of underground constructions. To fully understand the SCC and eventually avoid the occurrence of cable-bolt SCC in an underground reinforcement system, a dedicated testing system for investigating SCC in cable-bolt specimens was designed and constructed including long-term cable-bolt coupons and accelerated full-scale cable-bolt tension-loading apparatus. Both “long-term” tests using simulated underground environments and “accelerated” tests using an acidified solution were conducted. After the tests, the corrosion patterns and fractographic features of the specimens were observed and analyzed.A wide range of cable bolts have been developed including plain cable bolts, bulbed cable bolts, and bird-caged cable bolts with both plain and indented wires. Different types of cable bolts are designed for application in different geological and geotechnical conditions. For example, the cable bolt with indented wires was designed to increase the bond strength between the cable and grout interface. The number of cable wires, wire arrangement, and geomoetry are different in different types of cable bolts. Superstrand and TG bolts are representive of the common characteristics of different types of cable bolts. Superstrand is solid and the TG is hollow. The nubmer of wires and wire arrangement of the cable bolts are shown in Cable bolts consist of multiple individual wires that are wound together in a certain manner. To further characterize the material and mechanical properties of cable bolts, the chemical compositions and mechanical properties of the central straight wire of Superstrand with the diameter of 6 millimeters was analyzed . The strASTM G39  recommenCable-bolt SCC often occurred in the strata with clay bands and groundwater which suggested mineralogical-influenced corrosion was one potential factor causing the SCC failure . TherefoAfter the preparation of the long-term cable-bolt coupons, all the specimens were cleaned with acetone, labelled, and weighed. The loaded specimens were then immersed into the “corrosion cell” with different packing medium . The pacTo conduct SCC experiments on full-scale cable bolts, a tensile-loading apparatus was designed and constructed. The tensile-loading apparatus was composed of the loading frame, gripping system, and two guarding assemblies . The loaIn the tensile-loading system, a hydraulic cylinder and a mechanical nut retainment system were used to apply axial load to the cable-bolt specimens. The arrangement of the load frame, hydraulic cylinder, gripping system, and guarding assembly is displayed in The SCC experiments on Superstrands and TG bolts, made from plain and indented wires, were conducted under the periodically increasing strain-rate test conditions. In the periodically increasing strain-rate test, the axial deformation on the specimen was gradually increased at regular intervals for the duration of the test. Based on cable bolts’ mechanical properties, the axial strain rate applied on the specimens increased at 1.5% every day, while exposed to the acidified solution of two liters in the continuous cycling system. For each type of cable bolts, two cable-bolt specimens were tested to reduce the effect of scatter in the test results . The aciAfter exposure of 100, 200, and 300 days, one of the specimens was removed from each testing condition. The chemistry of the groundwater from each corrosion cell was analyzed after 300 days. The major cations and anion concentrations are illustrated in Different corrosion patterns were observed in different testing conditions . Slight All the full-scale cable-bolt specimens failed under the periodically increasing strain-rate test conditions while exposed to the acidified solution. An example of one failed TG bolt with indented cable wires is provided in The average times to failure of all the individual wires are displayed in The designed tension-loading system together with the application of the periodically increasing strain-rate methods provided a reliable and efficient platform for the SCC examination of the full-scale cable bolts. The test results indicated the number of wires and wire surface conditions in different types of cable bolt have direct effects on SCC susceptibility. Generally, the cable bolts with a greater number of cable wires provided higher resistance to SCC. For the same type of cable bolts, the cable bolts with indented wires increased its SCC susceptibility. Based on the test results, cable bolts with a greater number of plain wires are recommended to be used in the areas with high risk of SCC. The fracture characteristics of the failed cable bolts were examined to confirm the SCC occurrence. A typical step-shape fracture surface was observed on the cable wires from Superstrand with plain wires . It was The surface fractographic features of the cable wires were examined using the scanning electronic microscope (SEM). The fractographic characteristics observed on the Superstrand and TG bolts with plain wires were similar and consistent. SEM images of the fracture surfaces from Superstrand with plain wires are presented in The secondary region was following the SCC with some radial marks oriented towards this initiation area. Micro-voids and small ductile shear lip were observed in this region a. The trIt was noted that for cable bolt with indented wires, the crack initiated at the indented area . Even thA two-step methodology was implemented, including long-term cable-bolt coupon tests using mineralogical materials collected from underground mine and an accelerated full-scale cable-bolt test using an acidified solution. The results showed that mineralogical materials and applied stress intensity accelerated the corrosion process of the cable bolts. Localized corrosion observed on the specimens could induce local stress concentration at the bottom of the pits and accelerate the initiation of the cracks. The cable-bolt coupons can be used for detailed investigations into cable bolts SCC through field experiments. The designed full-scale tensile-loading apparatus and periodically increasing strain-rate method proved a platform for examining SCC of full-scale cable bolt. The number of wires and wire surface conditions in different types of cable bolt directly affected its SCC susceptibility. The cable bolts with a greater number of wires provided higher resistance to SCC. In terms of wire surface conditions, the indented cable bolts were more suspectable to SCC compared to cable bolts with plain wires. The cracks usually initiated at the indented area. The indentation reduced the wire cross-sectional area and increased the stress concentration at the indented area, which accelerated the initiation and propagation of SCC. Even though the application indentation improved the load-transfer ability of cable bolts, cable bolts with indented wires are not recommended to be used in the areas with high risk of SCC. These results can be used to design optimal support systems in different environmental and geotechnical conditions.


Endoplasmic reticulum (ER) stress triggers complex adaptive or proapoptotic signaling defined as the unfolded protein response (UPR), involved in several pathophysiological processes. Protein misfolding in the ER triggers the activation of three homologous transmembrane protein kinases, Ire1, the PKR-like ER kinase (PERK), and the transmembrane transcription factor ATF6. Protein folding is highly redox-dependent; the relations between the generation of oxidative stress and ER stress have become very interesting fields for investigation. Evidence suggests that ROS production and oxidative stress are not only coincidental to ER stress but also integral UPR components. These components are triggered by distinct types of ER stressors and facilitate either proapoptotic or proadaptive UPR signaling. Thus, ROS generation can be upstream or downstream UPR targets. Pathways involved in unfolded protein response are important for normal cellular homeostasis and organismal development and may also play key roles in the pathogenesis of many diseases. This special issue intends to address the different aspects relating interaction between oxidative stress, UPR, and cellular redox capacity. We are grateful to the Editorial Board of Oxidative Medicine and Cellular Longevity, who devoted this special issue to UPR, and all authors for their contribution. Many manuscripts were submitted, and after a detailed peer review process, three high-quality research works and two reviews on topics of novelty were selected to be included in this special issue.2-O2) work in a similar way. S. Zhao et al. reported that H2-O2 mixture inhalation could protect against the cardiac dysfunction and structural disorders induced by ER stress in rats with chronic intermittent hypoxia (CIH). CIH is a consequence of obstructive sleep apnea—a common breathing disorder in humans. The authors found that H2-O2 improved cardiac dysfunction and attenuated CIH-induced ER stress by reduction of oxidative stress and cardiac apoptosis. An ER stress-oriented therapy is also used in cancer treatment. In the review by A. Walczak et al., the role of the ER-induced UPR pathway and the efficacy of its inhibitors and inducers in the inhibition of tumor progression are discussed. Correct protein processing and folding are crucial to maintain tumor homeostasis. Endoplasmic reticulum stress is one of the leading factors that causes disturbances in these processes. It is induced by impaired function of the ER and accumulation of unfolded proteins. Induction of ER stress affects many molecular pathways that cause the unfolded protein response. This is the way in which cells can adapt to the new conditions, but when ER stress cannot be resolved, the UPR induces cell death. The molecular mechanisms of this double-edged sword process are involved in the transition of the UPR either in a cell protection mechanism or in apoptosis. However, this process remains poorly understood but seems to be crucial in the treatment of many diseases that are related to ER stress.In the review by Y. Rellmann and R. Dreier, mouse models with specific changes in protein folding are described. The authors mainly focus on those mouse models with ER stress-related chondrodysplasia phenotypes. This is particularly important as UPR downregulate essential processes of the endochondral ossification including chondrocyte proliferation and differentiation and ECM protein synthesis. In consequence, autophagy and apoptosis are triggered and lengths of long bones are reduced. However, the detailed description of various mouse models with ER stress is particularly relevant for readers studying different aspects of the UPR. The authors review among others mice with a knockout of proteins involved in ER folding machinery, UPR signaling, degradation of aggregated proteins, and protein trafficking and secretion. These mouse models could be useful for the study of the molecular pathogenesis of various ER stress-related human diseases as well as to propose novel treatment schemes. One of the ER stress-related diseases is acute kidney injury. The accumulation of unfolded protein in ER in the kidney is observed in aging and during sepsis; however, the molecular background of kidney injury is different. The aged kidney has reduced UPR and elevated oxidative stress in comparison with a younger one. Along this line is the paper by X. Liu et al. The authors report the increased susceptibility of an aged kidney to ER stress with excessive reactive oxygen species level using a mouse model. This phenomenon is connected with the loss of PERK phosphorylation and XBP-1 mRNA splicing. They also compared the level of ER stress in an aged kidney with and without an antioxidant and found that the antioxidant prevented kidney function failure induced by severe ER stress. A similar protective function against ER stress-induced kidney injury showed methane-rich saline as reported by Y. Jia et al. They found that the ER stress in the kidney is a consequence of sepsis and it is connected with oxidative stress and the ER stress-related apoptosis. They measured histopathological damage, the levels of proinflammatory cytokines, and reactive oxygen species in kidney tissues and apoptosis ratio. Methane has anti-inflammatory and antiapoptotic properties and seems to be a good candidate for supportive treatment in sepsis; however, the molecular mechanisms of methane remain to be elucidated. 67% hydrogen and 33% oxygen mixture (HA. Walczak et al. discuss that the UPR involvement in the pathogenesis and progression of various types of cancer is presented. Since it is a very promising target for novel anticancer therapy, more and more new molecules are being tested. A significant amount of them is naturally occurring chemicals that are present also in plants. Due to the abundance of the compounds affecting UPR, A. Walczak et al. have summarized the literature review on tested modulators in various cancer cell lines. Thus, the UPR modulators are a promising hope for a personalized therapy for patients in whom chemotherapy or radiotherapy has failed. It can become an innovative way to fight several different types of cancer. The response to a given compound depends on the phenotype of tumor cells, the severity of the disease, and the chemotherapy used so far.The understanding of the ER stress response, especially in the aspect of pathological consequences of UPR, has the potential to allow us to develop novel therapies and new diagnostic and prognostic markers for cancer. It is emphasized that further experiments and analyses should be carried out using a variety of compounds that have the ability to inhibit and induce the UPR pathway in different types of cancers. It could also be useful in the treatment of noncancerous diseases including neurodegenerative disorders, i.e., glaucoma and Alzheimer's disease.