Since the critical care physician will most likely be involved in a life-threatening expression of systemic mastocytosis, recognition of this disease is of utmost importance in the critical care management of these patients. Mastocytosis is a severely under-recognized disease because it typically occurs secondary to another condition and thus may occur more frequently than assumed. In this article, we will review the current knowledge on the treatment of mastocytosis crises with an emphasis on critical care management. Mastocytosis is characterized by the clonal proliferation and accumulation of mast cells in different tissues. Mast cell mediators contain a wide range of biologically active substances that may lead to itching and hives but may ultimately lead to anaphylactic shock caused by the release of histamine and other mediators from mast cells. The mainstay of therapy is the avoidance of potential triggers of mast cell degranulation and, if unsuccessful, blocking the cascade of mast cell mediators. The critical care physician should be well aware of the special precautions which should be kept in mind throughout the management of a mastocytosis crisis to avoid massive mast cell degranulation. Histamine-releasing drugs and certain physical triggers like temperature change should be avoided. Mastocytosis is characterized by the clonal proliferation and accumulation of mast cells in different tissues, with a preferential localization in the skin and bone marrow. The clinical presentation of mastocytosis is heterogeneous, ranging from skin-limited to a more aggressive systemic variant . Mast ceThe incidence of mastocytosis has been estimated to be between 1:1,000 and 2:100,000, but several cases are not recognized as caused by mastocytosis . The preMast cells develop from pluripotent stem cells in the bone marrow and spleen. In mastocytosis, the majority of cases are associated with gain-of-function point mutations of KIT, a tyrosine kinase receptor located on mast cells. As a consequence, the receptor is continuously activated, leading to uncontrolled growth and activation of mast cells Fig.  2]. Mas. Mas2]. Mastocytosis is classified by the World Health Organization (WHO) in the category of ‘myeloproliferative neoplasms’ and can be subdivided into cutaneous and systemic mastocytosis and mast cell neoplasm Table . To estaStimulation of mediator release occurs by either IgE- or non-IgE-mediated mechanisms, including physical stimuli and drugs. The marked increased mediator release from the elevated mast cell numbers explains the much higher incidence as well as severity of anaphylaxis in mastocytosis patients as compared with the general population . SymptomAnaphylactic shock and complications are related to mast cell degranulation; that is, spontaneous bleeding may present features of mastocytosis , 16. WheIt is important to realise that, during further ICU treatment, patients with mastocytosis are inevitably exposed to triggers of mast cell degranulation, which may be followed by severe anaphylactic responses . When a When  intervention is planned during ICU admission, precautions must be taken. The anaesthetist should be conscious of the potential triggers and consequences of mast cell degranulation and be informed about the risk profile of the patient. Pre-medication may include benzodiazepines, H1- and H2-receptor antagonists to block the cascade of mast cell mediators, and glucocorticoids as anti-inflammatory and mast cell stabilizers. Because mast cell degranulation has been observed hours after trigger application, we recommend continuing medication for at least 4 hours after trigger application. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective prophylactic drugs because of their antiprostaglandin actions. However, they should be given only to patients who have received these drugs previously, as NSAIDs are also associated with serious anaphylactoid reactions .Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells in different tissues. After trigger application, an overwhelming release of mast cell mediators may lead to severe haemodynamic compromise and multi-organ failure. Knowledge of the pathophysiology of the disease is of paramount importance for adequate treatment and the prevention of secondary events of mast cell degranulation due to mechanical or pharmacological triggers. During treatment, physicians should avoid potential triggers of mast cell degranulation, consider giving pre-medication before interventions, and be aware of and prepared for the clinical manifestations caused by mast cell mediators. Avoiding medication and physical stimuli that trigger histamine release and blocking the cascade of actions of mast cells constitute the mainstay of therapy besides treatment of anaphylaxis.


Saam acupuncture is one of the original therapeutic modalities representing traditional Korean medicine. It was originally described in a manuscript that is estimated to be published at some point between 1644 and 1742, in the middle of the Cho Sun dynasty, by a Korean Buddhist monk whose name is unknown. The principle of combining five shu points is based on the theory of Nan-jing. The treatment and diagnosis concepts in Saam acupuncture were mainly influenced by Dongeuibogam and Chimgoogyeong-heombang. The basic characteristic of combining five shu points in Saam acupuncture is the selection of the tonification and sedation points along the self-meridian and other meridians based on creation and governor relationships. Saam acupuncture clinical studies have mainly focused on musculoskeletal pain and autonomic nervous system regulation. From a neurophysiological perspective, Saam acupuncture, which involves five shu points as the main treatment aspect, has the advantage of increasing parasympathetic nerve activation and adjusting the balance of the autonomic nervous system. Inserting a needle into the skin layer while considering the respiratory phase and stimulating the needle gently and lightly could maximize the effect of Saam acupuncture. The specific Saam acupuncture prescribed should be identified on the basis of the neurobiological perspective. Saam acupuncture, which is one of the original therapeutic modalities representing traditional Korean medicine, is a unique treatment method that has a different origin than the modalities from China and Japan. The basic characteristic of combining five shu points in Saam acupuncture is the selection of the tonification and sedation points along the self-meridian and other meridians based on creation and governor relationships. In China, five element acupuncture, tonification, and sedation points along only the self-meridian are selected. Japanese meridian therapy added source point, connecting point, cleft point, alarm point, and transport point on the basis of Korea Saam acupuncture conception of the combined five shu points .Saam acupuncture is based on the traditional concepts of yin-yang, five elements, ZangFu (viscera and bowels), qi, and meridians. Saam acupuncture treatment cannot be separated from these viewpoints. In particular, it involves the application of five shu points according to the creation and control cycles of the five-element theory. Therefore, the combination of acupoints in Saam is easier to understand from the perspective of traditional medicine.The meridian is divided into three parts: the arm or foot, three yin and yang, and six ZangFu parts. A total of 24 deficiency and excess symptoms, with 24 coldness and fire symptoms, exist across the 12 meridians, but the diagnostic criteria related to these symptoms are too ambiguous for selecting a correct meridian. Except for the regular 48-treatment protocol, the treatment strategies are largely variable. Efforts were made to produce Saam treatments that are more effective by including other acupoints, with the main points firmly based on the regular pattern [Various Korean scholars have suggested different methods for applying Saam acupuncture in the clinic. Lee  proposedHowever, a description of the mechanism of acupuncture to both clinicians and patients in mainstream medicine by using the contemporary concepts of neurobiology would be helpful for incorporating Saam acupuncture into mainstream medicine . An impoIn this paper, several neurobiological mechanisms of Saam acupuncture treatment are presented from the perspective of the clinician. Saam acupuncture clinical trials are also discussed. Further, the historical background of Saam acupuncture and the basic principle of combining acupoints are briefly reviewed.The original manuscript that described Saam acupuncture is estimated to have been published between 1644 and 1742, in the middle of the Cho Sun dynasty, by a Korean Buddhist monk whose name is unknown. Because Chimgoogyeong-heombang , which was published in 1644, is quoted in the manuscript of Saam acupuncture, the publication period of the Saam acupuncture manuscript can be estimated to be after 1644 . After 1Viscera/bowel-based acupuncture was developed in Chimgoogyeong-heombang , with integration of the meridian/exterior theory with the viscera manifestation theory, which in turn provided various methods for viscera diagnosis. Viscera identification became the basis of Saam acupuncture treatment .The Dongeuibogam (Treasured Mirror of Eastern Medicine) contains the following phrase: “One acupuncture needle in all the diseases, up to within four acupuncture needles, acupuncture on the whole body is not a good idea.” This phrase represents the characteristics of the traditional Korean acupuncture method. In this context, Saam acupuncture treated the disease within four acupuncture points. Further, an acupuncture method based on the five element principles is presented in the acupuncture section of the Dongeuibogam. The idea of treating a disease derived from viscera/bowel dysfunction by using five shu points influenced Saam acupuncture .The following phrase is taken from the 69th chapter of Nan-jing: “In the case of depletion, fill the respective mother, in the case of repletion, drain the respective child, one must fill the first and then drain afterward.” Gao-Wu, of the Ming Dynasty of China (1519 A.D.), was the first acupuncturist to describe the use of tonification and sedation points along the self-meridian by using the five shu points according to the 69th issue of Nan-Jing. Zhang Shi Xian advocated the use of five shu points in other meridians in Jiao Zheng Tu Zhu Nan Jing (Illustrated note of Classic of Difficult Issues) . On the In Saam acupuncture, the relationship with the governor is important, as is the relationship between the mother and son. The governor is sedated under the condition of deficiency and is tonified under the condition of excess .The basic rules are those of the creation and governor relationships. In the case of insufficiency of any meridian, the mother points of its mother and its own meridians should be tonified and the governor points of its governor and its own meridians should be sedated. For example, the following is applied if the lung meridian is diagnosed as deficient: earth tonification, lung meridian-earth point LU9 and spleen meridian-earth point SP3 and fire sedation, lung meridian-fire point LU10, and heart meridian-fire point HT8 . The othIn the case of the excess of any meridians, the governor points of its governor and its own meridians should be tonified and the son points of its son and its own meridians should be sedated. For example, the following is applied if the lung meridian is diagnosed to be excessive: fire tonification, lung meridian-fire point LU10, and heart meridian-fire point HT8 and water sedation, lung meridian-water point LU5, and kidney meridian-water point KI10 .Another simple but rarely used one is coldness-fire acupuncture treatment derived from the deficiency-excess acupuncture treatment. For cold symptoms, the fire points of its own and the fire meridians are tonified and the Water points of its own and the water meridians are sedated. For heat symptoms, the water points of its own and the water meridians are tonified and the fire points of its own and the fire meridians are sedated .Among the clinical case studies of Saam, 85% used either a tonification or a sedation formula, whereas 15% used variations of the tonification and the sedation formulae . Saam trTo review clinical articles on Saam acupuncture, we used the following six databases: “Korean Studies Information Service system (KISS)”, “National Discovery for Science Leaders (NDSL),” “Research Information Sharing Service (RISS),” “Oriental Medicine Advanced Searching Integrated System (OASIS),” PUBMED, and Google Scholar. The key words were “Saam” and “Saam acupuncture.” The retrieved papers were screened so that only articles related to clinical research were retained. We selected 28 case studies and 17 clinical studies.Saam acupuncture has been applied for several diseases, and these are summarized in In the case of a sleep disorder caused by a traffic accident, tonification of gall bladder improved sleep quality . In tradModified Saam acupuncture was used to treat 17 patients with refractory, sudden sensory-neuronal hearing loss of more than 3 weeks after a failed trial of conventional treatment including corticosteroids. The total improvement rate at 70.4 days after the initial visit was 47.1%. Thus, Saam acupuncture might be effective for refractory sensory-neuronal hearing loss in which conventional therapy has failed .A 30-year-old woman with a right adnexal mass was treated with Saam acupuncture for 14 weeks. After treatment, transvaginal sonography revealed disappearance of the right adnexal mass. This effect may have been evoked by modification of autonomic nerve activity as a result, for example, of reflex alteration of ovarian sympathetic nerve activity .Modified Saam acupuncture  was used to treat 10 cancer patients for 2 weeks with 4 sessions. CD3+, CD8+, and T-cell subsets were significantly increased and the fatigue severity scale score was significantly decreased. Therefore, Saam acupuncture may improve the immune system .2) was significantly increased in 18 amyotrophic lateral sclerosis patients with respiratory dysfunction who were treated with lung tonification [Finally, peripheral capillary oxygen saturation  –28, the Although the method of setting the test and control groups differed slightly for each study, the use of a sham needle device for the control group appears to be the most desirable condition for scientific research. The Park sham needle was used to blind the participants , and theComparing the simultaneous application of Saam acupuncture and general body acupuncture and a single application of general body acupuncture is not suitable –22 becauSaam acupuncture principally uses the acupoint below the elbow and knee joint. The five shu points occupy large areas in the cortical representation in the postcentral sensory gyrus in the brain. Cho et al.  stated tAcupuncture likely has an effect on homeostasis via the somatic autonomic reflex . This hoSato  showed tNishijo et al.  revealedAcupuncture stimulation on the abdomen impedes gastric motility . StudiesThe effect of acupuncture stimulation varies depending on the depth of the insertion, the respiratory phase, stimulation dose, and observation period. Mori et al.  showed tHaker et al. showed that stimulation of the thenar muscle (LI11) resulted in a significant increase in sympathetic and the parasympathetic activity during the stimulation period and during the poststimulation period. A significant decrease in the heart rate at the end of the poststimulation period was also demonstrated. Superficial needle insertion into the skin overlaying the right thenar muscle caused a pronounced increase in the balance of both the sympathetic and parasympathetic activities during the 60 min poststimulation period .Tanaka et al. demonstrated that SES  stimulation significantly decreased headache intensity, with a strong trend towards decreasing static electromyography (EMG) activity compared to CONT (without considering the respiratory phase) stimulation . This suIn the neurobiological model, point specificity does not appear to exist with regard to musculoskeletal action, but five shu points, including PC5, PC6, and ST36, have some point specificity with regard to systemic action at the brain level. This acupuncture-point specificity has been attributed to the presence of a deep nerve . HoweverThe Saam acupuncture method includes a variety of combinations of five shu points, and each combination is believed to have a distinct effect. However, the specificity of each Saam acupuncture treatment has not been yet identified from a neurobiological perspective. Therefore, when applying Saam acupuncture in the clinic as medical acupuncture, an approach that focuses on the balance and homeostasis of the autonomic nervous system appears to be desirable. Further, revealing the difference between the Yin meridian and Yang meridian treatments, which are anatomically divided into the medial and lateral sides of the body, is necessary from the viewpoint of the neurobiological mechanism.The original Korean acupuncture method, Saam acupuncture, was invented 400 years ago by a Korean Buddhist monk based on the foundation of Dongeuibogam and Chimgoogyeong-heombang. He embodied Nan-jing's theory as an acupuncture treatment. Because Saam acupuncture was created on the basis of the theory of oriental medicine, approaching Saam acupuncture in the clinic via the oriental medical diagnosis is easy. However, for Saam acupuncture to be recognized as a medical acupuncture and to be used as a universal treatment in many countries, the mechanism of Saam acupuncture should be explained through scientific verification. Saam acupuncture, which operates with five shu points as a main aspect of treatment, has the advantage of increasing parasympathetic nerve activity and adjusting the balance of the autonomic nervous system. To maximize this effect, inserting a needle into the skin layer and providing gentle and light stimulation while considering the respiratory phase may be desirable.


The substantial impact of cross-border collaborative control efforts on the burden of malaria in southern Africa has previously been demonstrated through the successes of the Lubombo Spatial Development Initiative. Increases in malaria cases recorded in the three partner countries  since termination of that programme in 2011 have provided impetus for the resuscitation of cooperation in the form of the MOSASWA malaria initiative. MOSASWA, launched in 2015, seeks to renew regional efforts to accelerate progress towards malaria elimination goals already established in the region. National malaria programmes, together with developmental partners, academic institutions and the private sector seek to harmonize policy, strengthen capacity, share expertise, expand access to elimination interventions particularly amongst migrant and border population groups, mobilize resources and advocate for long-term funding to ultimately achieve and sustain malaria elimination in the MOSASWA region. Cross-border malaria control initiatives are important to supporting malaria elimination efforts, especially when low transmission countries share borders with higher transmission countries. The World Health Organization (WHO) Global Technical Strategy (GTS) 2016–2030 . South APlasmodium falciparum, with Plasmodium malariae and Plasmodium ovale also occurring in Mozambique. Anopheles arabiensis and Anopheles funestus represent the primary vectors in all three countries [The MOSASWA region consists broadly of eastern Swaziland, the southern Mozambican provinces of Maputo, Gaza and Inhambane, and the north-eastern districts of the South African provinces of KwaZulu-Natal, Mpumalanga and Limpopo Fig. . The regountries .Fig. 1ThTransmission in South Africa and Swaziland is seasonal, peaking between November and April, and is unstable and epidemic prone, but is stable and year-round in Mozambique.Baseline incidence rates of 2.64 cases per 1000 population at risk in South Africa, 2.34 in Swaziland and 219 in Mozambique were recorded in 2014 at the commencement of the MOSASWA initiative ; howeverMozambique has traditionally not implemented widespread indoor residual spraying (IRS) due to financial and logistical challenges, and has also prioritized its resources for the higher transmission and more populous north. Conversely, South Africa and Swaziland have invested heavily in the scale-up of IRS towards the goal of zero local transmission , 11. HowThe MOSASWA initiative is being built on the foundations of the Lubombo Spatial Development Initiative (LSDI), established in 1999 to address the issue of high malaria transmission in an area targeted for accelerated agricultural and economic development . The priAn increase in the burden of malaria in all three countries has been noted since the closure of the LSDI in 2011, despite sustained in-country implementation of malaria interventions in South Africa and Swaziland. Comparison of case counts recorded at baseline prior to the implementation of the LSDI (1999) with those observed at project termination in 2011 and again in 2014 just prior to the establishment of MOSASWA, reveals that gains achieved by the LSDI have been eroded subsequent to project termination in 2011 . ConsequFollowing the successes recorded by the LSDI, the impact of cross-border collaboration on regional malaria burden has been recorded through several other international initiatives, including the 13-country Asia-Pacific Malaria Elimination Network (APMEN) established in 2009 , the 11-The MOSASWA malaria initiative has received political support from each of the participating countries through the signing of a declaration committing them to tackling malaria, particularly in the shared border areas of each country . The goaSome 18 key strategies are identified under the four objectives outlined in the MOSASWA Strategic Plan 2016–2020 . BroadlyThe MOSASWA initiative is built on the solid foundation of the LSDI, from which capacity still exists in all three affected countries for implementation of strategies and management of the initiative. Although malaria cases in the MOSASWA region increased in the 2012–2015 period, numbers remain relatively low. Every effort needs to be made to reverse the recent trend, to bring these areas back onto the elimination trajectory.Financing required for the MOSASWA initiative to implement its 2016–2020 strategic plan is in the region of 39 million US$. Funding for this initiative, albeit challenging, will need to be sourced via domestic financing mechanisms to ensure sustainability.MOSASWA forms part of the broader Elimination Eight (E8) malaria initiative consisting of collaboration amongst eight southern African countries. The goal of the E8 initiative is to enable and accelerate toward zero local transmission in the four front-line countries  by 2020 and achieve the same in the second-line countries  by 2030 . RegionaEach of the three partner countries is pursuing aggressive malaria control and elimination interventions with the common eventual goal of eliminating malaria. Specific challenges exist within each country’s individual borders, varying with the respective epidemiology, intrinsic receptivity, and funding landscape of each, and successful elimination will require efforts across all programme areas. Many of these challenges will need to be met by the individual countries. However, malaria transmission dynamics amongst these countries are highly connected and interdependent, being linked through population movement and malaria ecologies. Hence, it is in the collective best interest to operationalize cross-border collaboration to reduce the impact and burden of malaria locally and trans-nationally. The MOSASWA initiative will require that best practices and lessons learnt from the LSDI be effectively applied in order to assure a sustained long-term effort wholly owned by the MOSASWA countries.The MOSASWA initiative comes at an important stage in the malaria elimination efforts of Swaziland and South Africa. For these two countries to have a realistic chance at elimination, neighbouring Mozambique’s collaboration will be pivotal. Further, escalation of control efforts in Maputo Province will ensure its own accelerated transition towards elimination.Over the past decade, all three participant countries have achieved substantial reductions in their malaria burden. In South Africa and Swaziland, malaria is now limited to border districts and malaria cases among migrant populations represent a high proportion of the total number of recorded cases. Mobile populations pose the greatest challenge to achieving malaria elimination. As has been observed post-termination of the LSDI, movement of people from high-transmission areas to areas with very low transmission results in an increase in the number of malaria cases in the host country or region. Progress towards malaria elimination in these countries will require improved access to health services for these groups. As the southern African region moves towards malaria elimination, ministries of health need to ensure that migrants, refugees and mobile populations have adequate access to prevention interventions as well as prompt diagnostics and effective treatment. This ideal is enshrined within the MOSASWA strategic plan.The MOSASWA initiative is an adjunct to country pre-elimination and elimination efforts. Swaziland and South Africa’s reduced malaria case numbers places these countries firmly in the elimination and pre-elimination phases, respectively, however it is imperative that malaria interventions are optimized across their borders with Mozambique to give these countries a real chance at elimination of the disease. Whilst migration and cross-border movement of persons is a direct focus area of MOSASWA, in-country activity will not diminish. Surveillance, screening and treatment, together with effective vector control, will be the key drivers to removing malaria reservoirs in eliminating countries. The most serious threat to malaria elimination is not resurgence due to insecticide or drug resistance, but non-implementation of effective interventions due to non-sustainable funding. Sustained, adequate funding is necessary to maintain the gains made in the control phase and access to increased funding is necessary as countries progress towards elimination. As evidenced post termination of the LSDI, gains achieved over decades can be eroded in a matter of months when preventative and curative processes deteriorate. The MOSASWA initiative, through sound political commitment, is pursuing funding for the start-up phase of the first 3 years. Thereafter, it is up to domestic funding together with private–public partnerships to warrant that the initiative is well funded and that the gains made in the fight against malaria are maintained through to elimination . The MOS


The increasing levels of drug resistance are one of biggest threats to overcome microbial infection. The ability to rapidly and accurately detect a given pathogen and its drug resistance profile is essential for the appropriate treatment of patients and for preventing further spread of drug-resistant strains. The predictive and informative value of these molecular markers needs to be translated into robust surveillance tools that correlate to the target and extent of resistance, monitor multiresistance and provide real time assessment at point-of-need. Rapid molecular assays for the detection of drug-resistance signatures in clinical specimens are based on the detection of specific nucleotide sequences and/or mutations within pre-selected biomarkers in the genome, indicative of the presence of the pathogen and/or associated with drug resistance. DNA and/or RNA based assays offer advantages over phenotypic assays, such as specificity and time from collection to result. Nanotechnology has provided new and robust tools for the detection of pathogens and more crucially to the fast and sensitive characterisation of molecular signatures of drug resistance. Amongst the plethora of nanotechnology based approaches, gold nanoparticles have prompt for the development of new strategies and platforms capable to provide valuable data at point-of-need with increased versatility but reduced costs. Gold nanoparticles, due to their unique spectral, optical and electrochemical properties, are one of the most widely used nanotechnology systems for molecular diagnostics. This review will focus on the use of gold nanoparticles for screening molecular signatures of drug resistance that have been reported thus far, and provide a critical evaluation of current and future developments of these technologies assisting pathogen identification and characterisation. Rapid and specific detection and characterisation of agents involved in infection is of paramount importance to deliver successful treatment. Traditional methodologies for identification of pathogens, though of extreme relevance, may be laborious and time-consuming, which may lead to delayed definitive diagnoses and treatment to the patient . SeveralChlamydia sp. and Gonococci. Introduction of PCR allowed the development of a plethora of diagnostic approaches for clinically relevant bacterial pathogens , specifically five genotypes corresponding to sensitivity to rifampicin and four resistant genotypes. While there is great potential of molecular assays to increase the speed and accuracy of bacterial identification in the clinical laboratory, limitations of NATs must be considered. For example, sample preparation and DNA purification from complex media constitutes a serious drawback for these assays since quantity and quality of template/target is one of the main aspects that affect performance. Also, costs associated to specialized training for personal and sophisticated equipment pose a serious obstacle for the widespread implementation of NATs as front line diagnostics.Nucleic acid-based tests can be used to detect the presence of organisms directly in clinical specimens without the need of culture. In addition, hospital infection control and epidemiology programs are benefiting from the use of NATs for detecting antibiotic resistance genes and for subtyping bacteria. The first NAT cleared for use by the Food and Drug Administration (FDA) was the Gen-Probe PACE test (1988) that used nucleic acid hybridisation to detect athogens . One sucIn the last decade, the use of nanomaterials for biosensing has been having a great impact and presents a great opportunity to develop fast, accurate and cost effective approaches for detection of pathogenic infectious agents. Nanodiagnostics have focused on the design of systems where researchers manipulate the properties of nanostructures for diagnostics purposes. Compared to standard methodologies, nanotechnology based approaches have several important practical advantages, including: enhanced surface reactivity, quantum confinement effects, enhanced electrical conductivity and enhanced magnetic properties, which enable nucleic acid detection to be extremely sensitive . It shouDespite the wide range of nanoscale systems for biomolecular assays , the mosFigure 1; Gold nanoparticles have unique optical properties associated with a well-defined surface plasmon resonance (SPR) band in the visible region of the spectrum , stronglIdentification of pathogens based on specific target sequences has become the corner-stone of molecular based approaches to discriminate between organisms and characterize particular variations at the genomic level that provide unique nucleic acid signatures suitable for diagnostics. This trend has had a new surge with the development of numerous nanoparticle-based approaches designed to identify those pathogen signatures with extra sensitivity and faster than ever before . In factThe first proof-of-concept for nanodiagnostics using AuNPs was introduced by Mycobacterium tuberculosis (Mtb). The method consists in differential stabilization of Au-nanoprobes in presence of DNA targets following salt induced aggregation: presence of a complementary target prevents nanoprobe aggregation and the solution remains red; whereas non-complementary/mismatched targets do not prevent gold nanoprobe aggregation, resulting in a visible change of color from red to blue. The methodology was tested in clinical samples demonstrating high efficiency with results comparable to those attained via commercial molecular tuberculosis (TB) diagnostics test, such as INNO-LiPA Rif. TB (M. tuberculosis complex (MTBC) and Mtb in 600 clinical strains.Following a similar technological approach,  Rif. TB . SimilarStaphylococcus aureus is also one of the most important human pathogens, causing more than 500,000 infections in the US each year , responsible for many opportunistic infections, enteropathogenic Escherichia coli, Mtb showing multidrug resistance (MDR-TB and XRD-TB), and Streptococcus pneumoniae. The prevalence of drug resistant strains of Mtb (MDR and XDR-TB) and MRSA have demonstrated the need for the development of drug susceptibility systems that are capable of delivering an unequivocal response to identify with high sensitivity and in a cost-efficient manner the pathogen’s resistance profile and allowing fast and accurate therapeutic approach . Rapid and cost effective diagnosis will have several benefits: earlier treatment of patients, reduction of time spent on inappropriate and ineffective treatment (thereby promoting the development of further drug resistance), and reduction of resistant strains spreading in congregate settings .Methicillin-resistant strains of  Kingdom . Current Kingdom . While a Kingdom . CombiniS. aureus strains back in 2004 via a colorimetric “spot- and-read” assay for the detection of mecA in MRSA genomic DNA samples. In this assay, nucleic acid targets are recognized by DNA-modified Au-nanoprobes that undergo a color change that is visually detectable when solutions are spotted onto an illuminated glass waveguide. This scatter-based method enabled the detection of nucleic acids while demonstrating a remarkable sequence specificity that allowed discrimination of single-base mismatches, deletions or insertions (S. aureus (MSSA) strains, where the detectable color change was observed only for MRSA with very short hybridisation times . This study was the first report on the use of AuNPs colorimetric assay for direct detection of MRSA in various types of clinical specimens  of the rpoB gene encoding for the beta subunit of RNA polymerase. Concurrent resistance to INH and RIF is commonly associated with point mutations in katG, inhA, and rpoB genes of MTBC  followed by a typical four month course of RIF and INH alone . Despitepatients . Resista of MTBC . Prompt  of MTBC .rpoB  allows for medium throughput analysis at a peripheral laboratory. A limit of detection could be set at 75 nM, however, for robust single base mismatch determination, 117 nM of DNA target were used per assay .Based on the differential non-cross-linking aggregation of Au-nanoprobes, Baptista’s group developed a simple and straightforward colorimetric method for Mtb identification and single base mutation discrimination in rpoB , which cinhA and rpoB genes in PCR amplified DNA from isolates. Using a multiplex PCR reaction, it was possible to assess both loci in parallel, and extend the potential of the Au-nanoprobe method to MDRTB molecular characterisation with special application in the most frequent Portuguese genotypes 15T and are amplified by a set of rpoB primer pairs flanking unique regions specific for MTBC members – first level of identification. The MTBC Au-nanoprobe constitutes a second level of identification. Another two sets of nanoprobes are used to discriminate the desired mutations. This approach brings new possibilities for MDRTB diagnostics as the Au-nanoprobe methodology may become an useful tool for MDRTB molecular characterisation at a point-of-need  have been used for almost 50 years presenting low sensitivity, specificity, and a high turn-around time. Although some laboratories use fluorochrome stains and liquid-based media for cultures, small hospitals or clinics cannot use these methods due to the need of high technical expertise, equipment, and expensive materials. The quality of sputum specimens and contamination of specimens due to inappropriate storage and/or long transport times to the laboratory has been a critical bottleneck .The development of complete, accurate and simple TB diagnostic tests able to target relevant TB sequences and assessing multidrug resistance cases has been one of the major bottlenecks for TB effective detection and treatment. Au-nanoprobes integrated within a paper-based platform may be proven to be an accurate, rapid, low-cost, and user friendly nanosystem for the identification of specific DNA sequences of TB, confirming infection and allowing identification of MDRTB strains. This nanosystem allows earlier treatment, reduction of time spent on inappropriate and ineffective treatment and reduction of MDRTB spread in congregate settings making it ideal for large screening and/or at point-of-need. The ability of coupling the LAMP amplification strategy to specific Au-nanoprobes translates into additional benefits: it eliminates the PCR amplification step bypassing the need of specialized machines and technicians, assessing multiple antibiotic resistances in the field and reaching remote communities.Integration of isothermal amplification techniques to AuNPs strategies. Isothermal amplification techniques have been recently developed as an alternative to PCR for target DNA amplification and detection without the use of a thermocycler  via serial transaminase measurements in patients on potentially hepatotoxic medications  is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care screening for DILI, Based on these principles new technologies were developed and are today available in the market. For example, Nanosphere offers two products approved by the FDA, one aimed at identifying typical mutations in coagulation factors without the need for nucleic acid amplification; another used to genotype polymorphisms associated with warfarin metabolism. In both cases the samples are processed through a cartridge where the sample analyzed via an automated processor and reader .Over the past decades, noble metal NPs, due to their optical and physic-chemical properties, have been used in proof-of-concept biosensing tools for the sensitive detection of pathogens of interest. Amongst these biosensing platforms, several have focused on the specific identification of DNA/RNA sequences associated to molecular signatures of infection and antibiotic resistance. AuNP based assays have progressively been integrated into sensing platforms capable of increasing sensitivity and lowering costs. Here, we provided an overview of existing strategies relying on the use of AuNPs for detection of molecular markers of antibiotic resistance. Despite the desperate need for robust, yet simple and cheap, screening tools to identify MDR pathogens, there are not that many concepts making it through to validation in the laboratory set. It is clear that microbiologists need to integrate the multidisciplinary teams that provide for nanodiagnostics development so as to widen the scope of combinations and modalities that can be easily coupled to current molecular nanodiagnostics technologies so as to facilitate integration to the lab and clinical setting.Detection strategies based on AuNPs provide comparable detection capability to that of standard techniques but at a fraction of cost and time, usually not requiring cumbersome sample preparation or equipment. As such, nanoparticle based approaches are expected to be incrementally applied to MDR characterisation and pathogen detection with particular emphasis for systems capable to operate at point-of-need. However, despite the massive investment in these technologies, translation to the clinics is yet to be fulfilled. Most of the reported systems in the literature still lack validation and/or are in pre-clinic stages with few commercially available products being available to the clinician. The next step is clearly to focus on the translation of some of the strategies that exist in the lab into the field and to the bedside.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 lesion originated around the postoperative bed, making the diagnosis challenging during the early course of the presentation. The case demonstrates giant cell tumor which originated in the metaphysis and subsequently grew to involve the epiphysis; therefore, early course of the disease not involving the epiphysis should not exclude this diagnosis. There have been only two previous reported cases of giant cell tumor around the fixation screws after bone-patella-bone anterior cruciate ligament reconstruction. This is the third reportable case where sequential images demonstrate development of a new giant cell tumor within the proximal tibia around the tibial screw. Retrospectively, image findings demonstrate classic features of giant cell tumor of the bone. However, the postoperative timing as well as the initial location of the lesion in the metaphysis with subsequent extension in the epiphysis made the diagnosis challenging for experienced musculoskeletal radiologists, as well as orthopedic surgeons in the early disease course. The case demonstrates and confirms the origin of the tumor in the metaphyseal region as previously suggested.A 26-year-old female sustained an injury to her right knee at a dance tryout. Radiographs and MRI were obtained for the evaluation of the acute injury Figures  and 2. IThe patient subsequently underwent an ACL reconstruction utilizing bone-patellar tendon-bone autograft at an outside institution with an uneventful recovery. The initial postoperative radiographs from the outside institution were unremarkable .Approximately 6 months after the ACL reconstruction surgery, the patient had reinjured her right knee from a slip and fall on the ice. Radiographs were obtained at this time , with thThe patient was referred to our tertiary referral center for further evaluation of the bone lesion and associated tenderness over the anteromedial aspect of the patient's knee in the area of tibial tunnel. Review of outside films by a musculoskeletal radiologist and an orthopedic surgeon in our center included a differential diagnosis of infection, benign fibrous lesion such as fibrous dysplasia, and nonossifying fibroma. At this point, the patient was lost for further follow-up at our institution due to combination of patient's status of serving in the military and living out of state. Approximately 1 year and 7 months after the ACL reconstruction, the patient was referred back to our tertiary referral center for further assessment and treatment of the medial tibial bone lesion. Radiographs and MRI from the outside institution Figures  and 7 shApproximately 3 months after the giant tumor curettage and cementation, MRI and CT were obtained as a baseline. These studies demonstrated a new area of uncemented intramedullary cavity anterior to the cement . Given tAs the lesion progressed, it became apparent that the radiographic and MRI features of the lesion are suggestive of giant cell tumor of bone. Our case demonstrates serial imaging of histologically proven new development of giant cell tumor of bone within the previous ACL reconstruction surgical bed. To our knowledge, there have been two previous case reports of giant cell tumor which have occurred in the proximal tibia and distal femur around the fixation screws after bone-patella-bone anterior cruciate ligament reconstruction , 2.The exact site of origin of GCT has been controversial. Murphey et al. suggest that GCTB likely arise from the metaphyseal side of the epiphyseal plate . The preWorld Health Organization (WHO) classifies giant cell tumor of bone (GCTB) as a benign, locally aggressive tumor. It is generally a benign, common bone tumor accounting for approximately 20% of benign osseous neoplasms, approximately 10% of primary osseous neoplasms, and 5% of all bone tumors , 4. TherConventional radiographs often have classic findings and can be highly suggestive of the diagnosis of GCBT. These findings include eccentric, lytic lesion centered in the metaepiphysis extending up to the subchondral bone plate without internal mineralization in a patient with closed physis . The marImaging differential diagnosis includes primary aneurysmal bone cyst (ABC) and chondroblastoma. Intravenous contrast administration on MRI is helpful in distinguishing GCTB with secondary ABC from primary ABC as the presence of enhancing soft tissue component is typically present in GCTB but not in primary ABC. Presence of extensive surrounding reactive edema within the marrow and soft tissues, sclerotic margin, and presence of chondroid matrix are helpful features distinguishing chondroblastoma from GCT. Additional differential diagnoses include metastasis, plasmacytoma, or multiple myeloma, which should be included based on patient's age, multifocality, and clinical history of known primary neoplasm. Telangiectatic osteosarcoma, giant cell-rich osteosarcoma, and fibroblastic osteosarcoma should be included in differential considerations when aggressive giant cell tumor of bone is suspected, as these subtypes of osteosarcoma do not produce osteoid matrix . FurtherIn the past, GCTB has been treated primarily by the means of surgical resection with curettage and placement of cement. Aggressive giant cell tumor may require wide excision and reconstruction utilizing modular endoprosthesis. Even with aggressive surgical treatment, the local recurrence rate was noted to range from 15 to 50% –6.


Introduction: There is paucity in the research on transfer validity of arthroscopic simulator training. The aim of this article is to determine whether skills derived from arthroscopic simulation are transferrable to the operating theatre and retained over time.Methods: A systematic review with rigorous criteria to identify the highest level of evidence available was carried out. The studies were critically appraised with narrative data synthesis.Results: Twenty-one studies on arthroscopic simulation were identified. Only two studies were randomised controlled trials. The first article demonstrated improved performance of basic knee arthroscopic tasks following a fixed period of training. The second article showed improved performance of arthroscopic tasks and no deterioration in the levels of skills following a period of six months. In addition, the two studies succeeded in demonstrating the importance of 3D motion analysis using computer simulators in the assessment of technical skills. Components of evaluation such as time to task completion, distance travelled by instruments and incidence of instruments collisions were associated with the highest validity and reliability of assessment. This systematic review highlighted the limitations of these two randomised studies.Discussion: Evidence from the two trials suggests that knee arthroscopy simulator training can result in improved performance. This review helped highlight the contribution of the two studies in terms of internal validity and consistency of using arthroscopic skills training. Further level I studies are however required to demonstrate the evidence for transfer and predictive validity of computer simulation as a training instrument. The aviation industry has often been proposed as a model for surgical training . Both diThe traditional model of one-to-one apprenticeship has trained successive generations of surgeons across the world and still prevails. In more recent times however the surgical community at large started to recognise the limitations of this traditional system, especially with the change from time-based to competency-based training and the pressures from health service providers . In addiWith an estimated incidence of 10 knee arthroscopic procedures per 10,000 population performed in the National Health Service (NHS) in England annually, there is clearly a need to consider the evidence for improved teaching modality for this specific skill set . Two rec®, EmbaseTM, CINAHL®  and the Cochrane Central Register of Controlled Trials (CENTRAL). Search date intervals included were from their year of inception to the last week of September ending 28 September, 2014 and limited to English language and humans. PubMed was used as the primary source and search engine for MEDLINE and MeSH  were used. The search terms included were: surgical trainees, surgery, orthopaedics, computer simulation, arthroscopy, skills and assessment. Alternative keywords, term variations and search strategy are outlined in A systematic review of the literature was performed according to the methods described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement . LiteratParticipants – limited experience orthopaedic surgical trainees, speciality trainees or surgical residents.Intervention – computer simulated arthroscopic surgery of the knee, including both diagnostic arthroscopic manoeuvres and simple therapeutic intervention such as resection of a torn meniscus.Comparison – standard case-based training under supervision of more experienced surgeons.Outcomes – transfer validity, 3D motion analysis and performance measured by standard assessment tools.The primary inclusion criteria for this review were studies, which looked at the use of computer simulators in arthroscopic surgical education among surgeons in training. Studies which looked at the use of haptic technology, and computer generated outcome data were included. This review focused on educational outcomes of training as surrogate for objective measurement of performance. Virtual reality motion analysis has demonstrated validity and reliability as an assessment tool for surgical skills across various specialities including arthroscopy , 23–25. As delineated by the research question, the focus of this review was on transfer of arthroscopic skills to the operating theatre and retention of these skills overtime. The principal exclusion criteria from this review were: case reports, technical reports, review articles and abstract only or conference proceedings publications. Equally, studies which looked at cadaveric models only, biomechanics, protocol and study design, and computer-assisted diagnosis or surgery were excluded. Similarly, studies on simulator-based assessment, validation of assessment tool, and studies without a comparison group, were excluded.©) and Warwick University library. References of full texts were also reviewed to identify any other potentially relevant study. The acquisition process of articles is outlined as a flow diagram in A rigorous systematic search was performed using the criteria outlined above. References were transferred into Endnote referencing software and duplicates were discarded. Firstly titles and abstracts were reviewed for relevance according to the research question. The remaining studies were analysed in their entirety. Access to full-text articles was obtained from Athens (EduservA total of 21 studies were generated from all the database searches. This yielded 16 titles for initial screening after removal of five duplicates. Following initial screening and application of the inclusion criteria three titles and 11 abstracts were excluded from the review. The numbers and reasons for exclusion following rigorous tiles screening, abstracts’ assessment and review of full texts are outlined in the flow diagram . The resHowells and colleagues  studied In this study closed randomisation methods with clearly established eligibility criteria were reported. The trial addressed a clearly focused issue, and assessed trainees belonging to the same institution hence minimising selection bias. In addition, the study was completed and no loss to follow-up was reported. The primary outcome measure was defined; however, there was no power calculation, a small sample size and unclear definition of the extent of prior arthroscopic experience. Furthermore, the outcome measures used were poorly validated. The assessment of competence by a senior surgeon may have potentially introduced observer’s bias and the assessment method had not been previously validated for the assessment of arthroscopic skills. The results lacked report of confidence intervals; and the untrained group had a narrower interquartile range in both results. This study in effect demonstrated improved acquisition of skills when comparing simulator training to no additional training.Jackson and colleagues  investigThis study utilised well-defined eligibility criteria and a distinct training protocol. In addition, it addressed a focused issue with a clear definition of all intervention and comparator groups. The participants received a standardised objective 3D motion analysis. The study sample was a good representation of trainee population and level of experience. Furthermore, the trial was completed with no report of loss to follow-up and all the clinically important outcomes were considered. Nevertheless, the authors did not report whether assessors were blinded to training status. Several other limitations can be highlighted from this article. A power calculation was not reported to establish the required sample size and clinically relevant differences in the outcomes. The primary outcome measure was not clearly defined and no report on whether any of the outcome measures were validated. The authors determined prior experience based on previous reports by candidates but no objective assessment of prior experience was identified as part of the study protocol. Similarly, the authors did not address the potential bias from the influence of other surgical experience gained during the study period.The annual report of 2009 from the Chief Medical Officer highlighted the importance of simulation in clinical training , 37. TheThe studies presented in this review sought to validate the use of computer simulation in arthroscopic training. Both studies were randomised single blind trials and used similar types of simulators and outcome measures. There were however discrepancies in their objectives and results. The study by Howells et al. demonstrated improved performance of basic knee arthroscopic tasks following a fixed period of simulator training. At the time of its publication this study was the only research looking at transfer and predictive validity of simulator arthroscopic training. The study by Jackson et al. also sought to demonstrate transfer and predictive validity of simulator training. This study had the particularity of looking at the retention of psychomotor skills over a pre-defined period of time. The authors not only demonstrated an improved performance of knee arthroscopic tasks but also no deterioration in the levels of skills attained following a period of six months. In addition, the two studies succeeded in highlighting the importance of 3D motion analysis using computer simulators in the assessment of technical skills. Components of evaluation such as time to completion of task, distance travelled by instruments and incidence of instruments collisions were associated with the highest validity and reliability of overall arthroscopic skills assessment. The two articles contribute to the body of evidence on internal validity and consistency of arthroscopic computer simulators shown in previous studies , 39.Howells et al. used an objective assessment of technical skills tool, a previously validated scale which was shown to correlate with motion analysis . This waThe two articles discussed here present multiple and recurrent limitations in their design, conduct and interpretation. Both studies had small sample sizes, which mitigate the generalisability of their results. The two groups of authors concentrated on knee arthroscopic skills, which render the results difficult to extend into other joint conditions commonly treated with arthroscopic procedures. Even though, previous studies showed internal validity of computer simulator in shoulder arthroscopic training . In addiIt has become clear that simulation plays an important role in the creation of the next generation of orthopaedic surgeons. The current climate of working time directives and expectations from the general public support the case for simulation training. The traditional model of “see one, do one, teach one” has therefore become no longer tenable, and it is considered inconsistent with the good clinical practice guidelines established by the General Medical Council . In addiFurther studies are therefore needed to investigate other training units, and other joints. Such research will also need to address other simulation-training models such as cadaveric labs as a potential stepping-stone for the transfer of skills from the computer simulator to the operating theatre. Future studies will need to employ validated outcomes measures pertinent to transfer and retention of skills, as well as longer-term evaluation of surgeons trained on simulators. Such research will also need to adjust for skill levels and clearly define the nature of on-going additional training the participants receive during the study period. In addition, the introduction of validated pre- and post-training evaluation tools can help reduce the risk of selection bias. Equally, a more robust link between the operating theatre and the simulation lab needs to be introduced in future studies, this can be performed with objective evaluation of trainees within real clinical setting prior to and following simulation training. A clear distinction between studies investigating the utilisation of computer simulators as an assessment tool or a training tool needs to be established. With the advent of personal communication devices the introduction of video assessment of trainee performing a surgical procedure can also help optimise the current model of procedure-based evaluation of surgical trainees. For instance, early work within other surgical specialities using Google Glasses™ as a training instrument promises to deliver satisfactory outcomes . UltimatHaptic technology and computer generated outcome measures have been shown to be valid training and assessment tools. This review helped highlight the contribution of the two studies in terms of internal validity and consistency of arthroscopic skills training using computer simulators. The two articles appraised add evidence of transfer validity to arthroscopic simulator training, and help build the case for further research in the field. Future studies of higher quality are therefore needed in order to address the limitations raised in this review. Due to the complex nature of skills and the impact on health service and patient safety, stricter research criteria need to be applied. Future work needs to incorporate assessment of cost-effectiveness, perceptions from trainers and trainees as well as the impact such training can have on curriculum design. The technology will inadvertently continue to progress alongside the availability of increasingly realistic simulators. It is therefore likely that continued research will further validate the field of simulation making it an integral part of clinical training and assessment. Equally, simulation will need to remain under strict professional scrutiny, to which all other aspects of clinical training are subject. Consequently, establishing a firm link between simulation and real clinical situations will be pivotal in sustaining this development. Future research, taking into consideration the vital elements raised from appraising the best available literature, will help provide better answers on the transfer validity of arthroscopic simulation training.The authors declare no competing interests. No external funding sources were received.


Antibiotic resistance is emerging as a potential threat in the next decades. This is a global phenomenon whereby globalization is acting as a catalyst. Presently, the most common techniques used for the detection of antibiotics are biosensors, ELISA and liquid chromatography—mass spectrometry. Each of these techniques has its benefits as well as drawbacks. This review aims to evaluate different biosensing techniques and their working principles in order to accurately, quickly and practically detect antibiotics in chicken muscle and blood serum. The review is divided into three main sections, namely: a biosensors overview, a section on biosensor recognition and a section on biosensor transducing elements. The first segment provides a detailed overview on the different techniques available and their respective advantages and disadvantages. The second section consists of an evaluation of several analyte systems and their mechanisms. The last section of this review studies the working principles of biosensing transducing elements, focusing mainly on surface plasmon resonance (SPR) technology and its applications in industries. Salmonella in the city of Montevideo, USA, causing the infections of 245 individuals between July 2009 and March 2010 [Antibiotics have been used extensively in the animal food industry since the early 1940s. The practice of using antibiotics in veterinary medicine has revolutionised the industry. Antibiotics are mainly utilized for the treatment of infection as a means for disease prevention (prophylaxis), such as treating respiratory and enteric infections during the early stage of the animals’ lives or for the treatment of bacterial infections, such as mastitis in the adult stage. Additionally, antibiotics are used as feed in sub-therapeutic concentrations to enhance growth . This isrch 2010 . UnfortuSalmonella enterica serovar Heidelberg and the commensal E. coli from retail chicken and human infections [E. coli is 32 times higher than that of non-poultry workers. Fifty per cent of poultry workers are affected by the colonization of gentamicin-resistant E. coli as compared to only 3% of non-poultry employees [The fast propagation of resistant bacteria is exemplified by the results of a recent Canadian study showing a strong relationship between the pathogen fections . The maifections . Evidencmployees . It is tmployees . This tymployees . With thTo reduce the risk of anti-bacterial resistance, the European Union instigated a “precautionary principle” model by banning certain antimicrobial growth promoters .For those antibiotics that are not banned, maximum residue limits (MRLs) of antibiotics have been set by both European countries and the United States to ensure the safety of consumers. According to the European Union’s definition, the MRL is the maximum legally acceptable amount of pharmacologically active substances  and their metabolites in foodstuffs originating from animals. The MRL is calculated with reference to the Acceptable Daily Intake (ADI), which includes a large safety margin in the calculation. For instance, the ADI for meat is about 500 grams per person. Those regulations are contingent upon the withdrawal period, which is the time period between the last dose of any pharmacologically active substance or of antibiotics in particular administered to the animal and the time at which the residue level in tissues  or products  is lower than or equal to the MRL. Withdrawal periods promote consumer safety by certifying that the MRL is not exceeded; they also ensure reinforced safety in case the MRL is not met . SeveralThe review is divided into three main sections: namely, an overview of biosensors, a section on biosensor recognition and a section on biosensor transducing elements. The first segment provides a detailed overview on the different available biosensing techniques and their respective benefits and drawbacks. The second section consists of evaluating several analyte systems and sensing mechanisms. The last section of this review focuses mainly on surface plasmon resonance (SPR) technology and its applications in industries.There exist several families of antibiotics: beta-lactams , chloramphenicols, tetracyclines, macrolides, lincosamides, spectinomycin sulphonamides, nitrofurans, trimethoprim, nitroimidazoles, polymyxins, quinolones and macrocyclics  .Fluoroquinolones (FQs) and sulfonamides (SAs) are the most popular antimicrobial agents used for the promotion of growth and for the treatment of infections due to their broad spectrum against both Gram positive and Gram negative microorganisms . Figure With the emerging concern regarding anti-bacterial resistance, several analytical methods have been developed to determine levels of antibiotic residues in meat products. The analytical methods for antibiotics detection can be divided into two groups, namely confirmatory and screening .Confirmatory methods depend on the properties of liquid chromatography alongside mass spectrometry (LC-MS) in the determination of the concentrations of analyte. Other detection methods include a combination of liquid chromatography and UV (LC-UV) or electrophoresis based approaches .Screening methods are primarily used to obtain semi-quantitative measurements. This approach is viable because of the low possibility of false-positive data, easy operation, quick analysis period, cost effectiveness and good selectivity. A biosensor is an instrumentation that comprises two key elements in close proximity: a transducing device and a recognition element with a supporting material. The recognition element consists of two affinity-pairing partners , one of which is immobilised .The transducer is utilized to detect any contacts between the affinity-pairing partners by converting the biological response into useful electrical signals. A processor then transforms the electrical signal  for inteThe simplicity of the mechanism of biosensors as compared to other detection techniques makes the detection of antibiotics with biosensors relatively fast, accurate and easy to implement. The primary limitation of biosensors is the uncertainty of the biological sensing element. For instance, the sensing mechanism may be affected by duration of use, type of molecules, and/or environmental factors . Another restriction of biosensors is the transducer size within the biosensors .Biosensors are grouped according to their signal transduction and their bio-recognition elements as illustrated in Biosensors are generally divided into three main types, namely: (1) electrochemical biosensors; (2) mass-based biosensors; and (3) optical-based biosensors. The working principles of each of the three biosensors are different and can thus be implemented in a variety of applications. The following section outlines different types of biosensors and offers a brief description of their working mechanisms.▪Potentiometric-based biosensors sense changes in pH and ion concentrations upon the antigen/antibody interaction.▪Amperometric-based biosensors sense the difference in current potentials during redox reactions when antigen/antibody pairing occurs.▪Conductometric/capacitive biosensors sense the change of electrical charge in a solution under constant voltage. This method is not recommended because of poor signal-to-noise ratio.▪Impedimetric-based biosensors sense changes in impedances upon antigen/antibody interaction.Electrochemical sensors  measure the electrical potential difference  caused by an interaction between an analyte and the membrane/sensor surface. There is proportionality between the electrical potential difference and the logarithm of the electrochemically active concentration of the material. Electrochemical biosensors provide high specificity with rapid analysis at a reasonable cost . There ePiezoelectric biosensors are considered as mass-based biosensors. Piezoelectric biosensors produce an electrical signal when a mechanical force is applied. They can be used for label-free detection of specific nucleic acid sequences for antibiotics detection in food. The most common type of piezoelectric biosensor is the quartz crystal microbalance (QCM) model. It uses specific oligonucleotides, which are restrained on the surface of the quartz crystal and inputted in a solution containing potential target nucleic acids, as illustrated in QCM operates at its optimal level if used with a molecular imprinting procedure. As the name states, this technique depends on molecular recognition whereby polymerization occurs around the target molecule. Consequently, this approach ensures that specific cavities are developed in the cross-linked polymeric matrices. This novel method can be used on polymeric nanofilms on the QCM sensor chip using a molecular imprinting approach, resulting in an enhanced real-time sensing platform .A recent development in antibiotics detection is the surface-enhanced Raman scattering (SERS) technique. The particularity of the SERS system is the addition of a metallic nanostructure to enhance weak signals and reduce the risk of fluorescence interference, as illustrated in Gold (Au) and silver (Ag) colloids of diameters 10 to 200 nm are the most common active substrates used in SERS’s nanostructure. Gold and silver are highly practical since they are inexpensive, easy to manufacture on a large scale and widely available. However, the main issue with both metals is poor performance in terms of reproducibility. This is due to the non-uniform aggregation of nanoparticles on the solid surface after the drying-up process. To remedy this problem, colloid-based substrates have been introduced. These include synthesis of multicomponent nanoparticles, such as Ag-coated (ferriferous oxide-core silica shell) composite microspheres. Subsequently, the sensitivity of the device has increased and the following antibiotics have been successfully detected: tetracycline, furadantin, furaltadone, ciprofloxacin, enrofloxacin and chloramphenicol . Despite1), cladding (n2) and jacket (n3), each with a different refractive index, as illustrated in Fibre-optic biosensors are considered as optical biosensors since they use the reflective properties of light to sense numerous analytes simultaneously. Fibre-optic biosensors consist of a core .A = Optical Absorbance.oI = Incident light intensity.I = Transmitted light intensity.є = Molar absorption coefficient.Lambert Beer Law used for absorptionThe use of fluorescence fibre-optic biosensors leads to the detection of signals by transferring the excitation light through an optical fibre; the emitted light is then measured via a detector. The change in fluorescence intensity is related to the analyte concentration. Fluorescence fibre-optic biosensors are a better option when compared to absorption sensors due to their ability to measure low concentrations of analyte .Luminescence fibre-optic biosensors detect the light emission from a chemical reaction whereby excited species return to the ground state. Luminescence fibre-optic biosensors can further be classified into chemiluminescence and bioluminescence . LikewisThe use of bioluminescence in performing tests to determine antibiotics levels consists of swabbing a sample and mixing it into a solution of luciferase/luciferin (enzyme/substrate). A summary of the reactions is illustrated below:Light is produced once luciferyl adenylate reacts with oxygen. Other products of this reaction include oxyluciferin and AMP .The main benefits associated with bioluminescence include high sensitivity, quick detection and easy implementation in portable devices .The drawback primarily involves the non-specificity of ATP assays as the latter is found in all living cells. To solve this problem, bioluminescence sensors are coupled with other sensors and detection techniques .The principle behind bacterial bioluminescence involves the transfer of the lux gene into the host bacterium in the case of an infection. The resultant reaction causes bioluminescence to occur; luminometers are then utilized to detect the emission of light , as illuFluorescence-based techniques are the most common techniques currently being implemented in biomolecular imaging due to their excellent sensitivity and selectivity, satisfying spatial and temporal resolution and cost effectiveness. Fluorescent biosensors are designed by synthetic receptors or biological macromolecular receptors, specifically proteins and aptamers. The designing of a fluorescent biosensor requires two key steps. The first step entails searching for a macromolecular receptor with optimal affinity and specificity to the target; the second step consists of integrating the receptor component and the signal transduction function such that an interaction between the macromolecule and the target induces a signal that can be captured by the transducer. However, an additional step consisting of integrating moieties, such as auto-fluorescent protein (AFP) or synthetic fluorophore, must be added since biological receptors lack signal transducing capabilities .Common AFPs, such as green fluorescent protein (GFP), can be found in jellyfish. The mechanism of AFPs consists of the exhibition of a spontaneous fluorescent emission in cells through the autocatalytic formation of the chromophore after translation. This procedure allows no interference of fluorescence properties or damage to cells since AFPs can be endogenously expressed through transfection of the plasmid DNA . AFP-basThe design of analyte-sensitive sensors is based on AFP variants, whose fluorescent properties are directly affected by the interaction between a target molecule and a chromophore moiety in AFP. Initially, pH and halide-sensitive AFP variants have been developed exploiting the intrinsic pH sensitivity of GFP mutants .Conformation-sensitive sensors operate when there is a conformational alteration of the receptor associated with the ligand-binding event, leading to the creation of a fluorescent signal response from AFPs. This conformational alteration characteristic ensures more versatility as compared to analyte-sensitive sensor given that it can sense more varieties of protein .Two primary factors dictate the performance of biological recognition elements (ligands) in biosensors. The first factor is the affinity and specificity of the ligands, which is determined by the ligand dissociation constant (Kd). The second factor involves the constrained shelf lives of the biorecognition elements .The two main techniques for recognizing antibiotics are the use of aptasensors and the use of antibody-mediated binding processes. Aptasensors can be defined as RNA- and DNA-immobilized aptamers (oligonucleic acids), which cause the binding of the analyte of interest to their respective 3D structure through ionic interaction, van der Waals forces or hydrogen bonds resulting in measureable signals. Aptamers are a preferred option for several applications due to their high binding affinity, easy labelling and high stability . From a et al. [One of the key developments in aptasensor technology is the combination and screening of tetracycline (TET)-binding aptamers via isothermal titration calorimetry, which is illustrated in et al.  showed eet al. . Howeveret al. . Anotheret al. .The second mechanism for the recognition of antibiotics involves antibiotics detection using antibody-mediated binding processes. This type of binding can be performed at the surface of the sensor for direct detection of the antibiotics or by inverting the assay and detecting the binding of antibody-spiked samples onto immobilized antibiotics in the context of a competitive assay .Apart from the two principles discussed above, the use of enzymes and the use of functionalised gold nanoparticles are new and innovative methods in the field . The intThe second type of optical biosensor is called surface plasmon resonance (SPR). Forty-nine per cent of the 60% of biosensors used for the detection or quantification of antibacterial or antimicrobial residues in the food industry operate under the SPR technique, as illustrated in 2 of material bound of surface area [Surface plasmon resonance is an optical transducer element and is commonly used in food safety. The principle behind the mechanics of SPR is illustrated in ace area .There are two main SPR assay formats for the detection of small chemical compounds. Smaller analytes are quantified using a competitive or inhibition assay. Competitive assays consist of a conjugated analyte being added to the sample and the latter competes to bind with the surface couple ligand. Inhibition assays consist of a fixed concentration of analyte binder that is added to the sample; the remaining free binding agent is captured by immobilizing analytes on the sensor chip .The design of SPR screening assays is based upon a competitive inhibition assay model whereby antibodies are used as biological recognition element. The preparation involves injecting a known concentration of drug-specific antibody mixed with the sample over the surface sensor chip with a drug derivative  immobilized onto it. In the absence of antibiotic residue in the sample, the antibody is able to bind to the immobilized antigen on the sensor surface, leading to the maximum value in SPR response units (RU). If antibiotic residue is present in the sample, the antibody binds to the antibiotic, inhibiting antibody binding to the derivative on the sensor chip surface and leading to a lower RU value. An increase in the concentration of the drug in the sample causes an increase in inhibition level and a lower SPR response, as illustrated in However, assays need to be optimized with regard to different parameters, such as antibody concentration, incubation time, pH and molarity of extraction/dilution, antibody/sample ratio and loading buffer, contact time, flow rate, and regeneration solution . In shorThe practicality and efficiency of SPR detection are notable, as illustrated in Microfluidics technology is a useful and increasingly popular tool used for the detection of analytes in several disciplines including food safety. Microfluidics technology is advantageous because of its ability to handle small sample sizes, which can be translated to less reagent wastage and quick detection. Additionally, microfluidics is utilized for point-of-care (POC) operations on sites due to its high level of efficiency and its reduction of the risk of cross-contamination. The new microfluidics technology has shifted into paper-based chips since there is no requirement for sample pre-processing. Moreover, there is no need for a power source to control fluid movement since the flow motion is influenced by capillary forces. The introduction of thermoplastic chips has also proven a viable option in terms of POC practices due to the disposability and cost effectiveness of the chips .The integration of microfluidics and fluorescent labels ensures a decrease in sample volume, which further results in a reduction in background signal noise. This ultimately increases sensitivity and signal-to-noise ratio, Raman scattering and Rayleigh stray light. However, the chip material must possess microscopy-compatible characteristics, such as being non-adsorbent to the molecules and having low auto-fluorescence.et al., the combination of gold nanoparticles and microfluidics resulted in a sensitivity of 150 times more than traditional ELISA method in the detection of interleukin-2 (IL-2). The cause for such a significant increase in sensitivity was the low sample volumes, which enabled the microfluidic device to increase the concentration and amplification of the signal from the gold particles [Microfluidics can also be incorporated with fluorescence resonance energy transfer (FRET) for the analysis of DNA. Microfluidics allows enhanced spatial and temporal resolution as compared to traditional fluorescently labelled molecules, as well as easy differentiation between hybridizing and non-hybridizing DNA oligomers. However, FRET-based techniques usually face problems of photo bleaching and pH sensitivity. To solve these issues, quantum dots (QD) are utilized for improved stability and signal. QDs’ ability to be bright and their extensive emission wavelength, which can be adjusted by altering their size and composition, make it possible to integrate them with microfluidics for antibiotics detection. The combination of QD + Microfluidics or QD + FRET or QD + FRET + Microfluidics ensures an amplified signal when sensing DNA and when detecting molecular size, binding and orientation. Gold nanoparticles are frequently used in antibiotics detection due to their easy conjugation to biomolecules, versatility in detection techniques and low toxicity. According to a study performed by Rivet, C articles .Digital microfluidics with SPR is practical for industrial use due to its high throughput screening abilities. This combination is also efficient since there is no requirement for labelling prior to analysis. Some of the drawbacks of this integration include the potential loss of native bioactivity of immobilized molecules, non-specific adsorption and the difficulty of functionalizing metal surfaces. Microfluidics can also be integrated with SERS detection. This combination results in constant uniform mixing conditions; very precise and reproducible results are also obtained. The main disadvantage of this method is the difficulty in the fabrication of consistent SERS enhancer nanoparticles and the cumbersome size of Raman instruments for detection. This technique however has already been commercialized for analyte detection for homeland security in the United States and in the recognition of cancer cells .The future of biosensors looks very promising with a total yearly investment in biosensor research and development accounting for USD 300 m (€236 m) . The funetc.) due to their smaller size and versatility. This particular technique involves using Solid Phase Extraction (SPE) and integrating it with Self Assembled Monolayer (SAM) cysteine (Cys) on gold nanoparticles since Cys is very stable and densely packed. As a result, the combination of SAMs and gold electrodes increases the sensitivity and selectivity and decreases the response time [Gold nanoparticles are another innovative new approach to detecting antibiotics in food residues. Primarily, SPR signals are amplified with the use of nanoparticles and the sensor sensitivity is thereby increased . Anothernse time .The use of label-free impedimetric immunosensors is another promising alternative since the labelling process is bypassed; the method also offers excellent sensitivity and fast response. Furthermore, the sol-gel-derived silica-based material integrated with impedimetric immunosensors ensures that biorecognition elements are encapsulated at low temperatures with satisfactory mechanical and thermal stability and that they experience insignificant swelling in aqueous solution .N-hydrosuccinimide (EDC/NHS) coupling techniques in several channels. Some of the indirect advantages of this system include the lack of a need for pre-processing of sample preparation and the good rate of repeatability with coefficient below 5% [Other alternatives include the combination of immunosensor-based recognition of antibacterials with a subsequent SPR-based detection to enhance the spectrum. This technology has been applied for the immobilization of chloramphenicol in pork and of streptomycin and dihydrostreptomycin in honey, milk and meat . The mosbelow 5% . The useIn conclusion, antibiotic resistance is becoming recognized as a threat capable of emerging within the next 20 years. This problem is not limited to certain countries but affects the whole world with globalization acting as a catalyst. Measures have been taken by European and North American countries to set up MRL standards. However, to further reinforce the safety of meat products, there is a need to detect the excessive use of antibiotics from the source (such as farm or slaughterhouse) such that unsafe products do not reach consumers. Concerns about antibiotic resistance have piqued the interest of researchers from various disciplines. Additionally, investors have injected millions of dollars into the development of new biosensing techniques.Presently, the most common techniques used to detect the presence of antibiotic residue are biosensor-based techniques, ELISA and liquid chromatography–mass spectrometry (LC-MS). Each of these techniques has benefits in terms of sensitivity and practicality as well as drawbacks, such as slowness and unsatisfactory cost effectiveness. This paper has provided a general overview of and comparisons between several biosensing techniques, such as electrochemical biosensors, mass-based biosensors and optical-based biosensors. There are numerous similarities and differences between biosensing mechanisms. For instance, most biosensors consist of a biorecognition element and a transducing element. However, they do not operate using the same principles or using the same recognition systems. It is to be noted that the recognition systems are equal in importance to the transducing element; both, therefore, should work in synergy for improved sensitivity. One recommended advancement would entail incorporating several biosensing techniques on one platform and using microfluidic chips to allow a merger towards the detection of multiple analytes from a single sample source. Overall, the field of biosensors consists of a broad spectrum with high potential for growth in the near future.


We investigate the interaction of visible light with the solid matters of semiconducting oxide nanorods (NRs) of zinc oxide (ZnO), indium tin oxide (ITO), and zinc tin oxide (ZTO) at the single nanomaterial level. We subsequently identify an intriguing, material-dependent phenomenon of optical rotation in the electric field oscillation direction of the scattered light by systematically controlling the wavelength and polarization direction of the incident light, the NR tilt angle, and the analyzer angle. This polarization rotation effect in the scattered light is repeatedly observed from the chemically pure and highly crystalline ZnO NRs, but absent on the chemically doped NR variants of ITO and ZTO under all measurement circumstances. We further elucidate that the phenomenon of polarization rotation detected from single ZnO NRs is affected by the NR tilt angle, while the phenomenon itself occurs irrespective of the wavelength and incident polarization direction of the visible light. Combined with the widespread optical and optoelectronic use of the semiconducting oxide nanomaterials, these efforts may provide much warranted fundamental bases to tailor material-specific, single nanomaterial-driven, optically modulating functionalities which, in turn, can be beneficial for the realization of high-performance integrated photonic circuits and miniaturized bio-optical sensing devices. Effective manipulation of optical and electro-optical signal is critical to the successful operations of optical modulators, switches, interconnects, and photodetectors in integrated photonic circuits and optoelectronic devices.In this Letter, we evaluate the light-matter interactions of technologically important semiconducting oxide nanorods (NRs) at the single nanomaterial level, while controlling key light-matter interaction parameters such as the wavelength and polarization direction of light, the NR tilt angle, and the analyzer angle. Pure and chemically doped NRs with comparable physical dimensions are systematically characterized for their material-dependent elastic scattering responses upon interactions with visible light. Specifically, we have chosen single NRs of ZnO as well as indium tin oxide (ITO) and zinc tin oxide (ZTO) due to their well-known functional benefits as lasers,E∥ (and E⊥ when the polarization direction is within (and perpendicular to) the plane of incidence, as illustrated in Figure Individual NR samples of ZnO, ITO and ZTO were synthesized by using a home-built chemical vapor deposition (CVD) reactor as reported earlier.o. The 3-dimensional (3D) contour plots simultaneously chart the scattering intensity, the position along the NR long axis, and the analyzer angle under the different incident light settings controlled by the wavelength and the polarization direction of the incoming laser. As reported earlier, the scattering response from individual NRs can either be continuous or discontinuous, depending on the NR tilt angle.o, the FDF scattering patterns from the ZnO NR are expected to be discontinuous, as shown in Figure E⊥ projected onto the sample plane, mimicking the highly localized scattering signal discretely monitored only at the two NR ends at high θ angles approaching 90o.Representative scattering data obtained from individual ZnO NRs are shown in Figures o, regardless of the incident polarization. In general, we also observe that the angle shift in the polarization oscillation of the scattered light becomes larger as the NR tilt angle of θ increases. And the polarization rotation effect in the scattered light occurs more pronouncedly on the ZnO NRs of the intermittent and discrete scattering natureFurthermore, careful examination of the ZnO NR scattering profiles in the 3D contour plots in Figure o ZnO NR unambiguously show the switching of the bright ends at different analyzer angles. For example, for the incident light setting of 488 nm and E∥, the left end of the ZnO NR scatters the strongest when the analyzer rotation is parallel to E∥. When the analyzer angle gradually increases, the left end of the NR scatters more weakly, while the scattering from the right NR end becomes stronger. When the analyzer angle is perpendicular to E∥, scattering from the left NR end significantly diminishes and that of the right end becomes intense instead. Similar trends are identified in all FDF scattering snapshots shown in Figure A series of images in Figure o for λ = 488 nm while that for the case of λ = 642 nm is approximately 10-25o. Therefore, our data indicate that the phase shift in the ZnO NR-triggered polarization rotation is expected to be higher for a light-matter interaction probed with a shorter wavelength of light. The observed rotation of the polarization from one end to the other end of the ZnO NR may be related to the doubly refracting nature of ZnO. The high birefringency of ZnO exhibits a difference of approximately 0.018 between the ordinary and the extraordinary refractive indices at the visible wavelength range.The set of 2D surface plots in Figure 2 and ZnO which, in turn, can serve as chemical and structural defect sites. Such chemical and structural perturbations may explain the absence of any phase shift in the scattered responses of the ITO and ZTO NRs seen in our experiments. Compared to the presence of optical rotation in ZnO NRs, no change in the oscillation directions of the scattered electric fields from ITO and ZTO NRs is observed, as depicted in the left panel in Figure We further examined other related nanomaterials for their scattering behaviors at the individual NR level and assessed whether a comparable polarization rotation effect is also present in doped variants of semiconducting oxide NRs. The typical FDF scattering plots from a single ITO and ZTO NR with comparable physical dimensions and light-matter interaction angles to those of the previously discussed ZnO NR cases are displayed in Figure Our findings may serve as a new guidance to tailor material-specific, single nanomaterial-driven, optically modulating functionalities in photonic and sensing devices. Our endeavors may be particularly valuable in developing biomedical sensors based on individual ZnO NRs by equipping them with additional modalities of polarization rotation and phase shift. In addition, with the demonstrated application of ZnO NRs as nanolasers and subwavelength waveguides,In summary, we have examined the light-matter interactions between visible light and the NRs of ZnO, ITO, and ZTO at the single nanomaterial level, while systematically controlling the key parameters such as the wavelength and polarization direction of light, the NR tilt angle, and the analyzer angle. We subsequently report the intriguing optical phenomenon of polarization rotation in the scattered light, which is confirmed to be present on the chemically pure and highly crystalline ZnO NRs, but absent on the chemically doped NR variants of ITO and ZTO with comparable physical dimensions and light-matter interaction geometries to ZnO. We further elucidate that the material-dependent polarization rotation of the scattered light is affected by the NR tilt angle, although the phenomenon itself occurs irrespective of the wavelength and incident polarization direction of the visible light for ZnO NRs.


Paget-Schroetter syndrome is a form of upper limb deep venous thrombosis usually seen in younger patients in association with repetitive activities of the affected limb. When occurring in more elderly patients or in those where it is difficult to appreciate a causative mechanism, other aetiologies should be considered. We present a case in which degenerative osteoarthritis of the sternoclavicular joint with osteophyte development impinged on the subclavian vein, leading to extensive upper limb thrombosis. The difficulties in identifying and managing this unusual cause of Paget-Schroetter are presented and discussed. Paget-Schroetter Syndrome is a deep venous thrombosis (DVT) of the subclavian-axillary vein complex usually seen in association with repetitive upper limb activity . AnatomiA 69-year-old former competitive rower and active sportsman presented to the emergency department with a 10-day history of pain and increasing swelling to his left arm. His background history included hypertension and paroxysmal atrial fibrillation. Physical examination revealed a neurovascularly intact left arm with extensive swelling distal to the axilla. No other abnormality was detected on physical examination. The patient was left-handed. Venous duplex ultrasound demonstrated occlusive thrombus in the left upper limb venous system involving the proximal subclavian, axillary and basilic veins, and the brachial veins to the level of midhumerus. Laboratory testing showed no evidence of a coagulation disorder.Contrast venography confirmed thrombus extending from the brachial vein to the left brachiocephalic vein . MechaniFollowing thrombolysis, the patient underwent a left-sided transaxillary first rib resection to decompress the thoracic outlet with the aim of subsequently placing a stent across the affected portion of subclavian vein. During stent placement, performed 10 days after his first rib resection, the patient's left-sided central veins had again thrombosed, necessitating further mechanical thrombectomy to restore patency. A venous stent was then placed at the level of venous stenosis with poststenting venography, demonstrating a widely patent vessel. The patient was discharged on oral anticoagulation therapy.The patient was symptom-free at his 3-month follow-up; however, a CT at that time demonstrated compression of the subclavian vein stent with significant architectural distortion. The causative mechanism of this impingement was a large osteophytic projection arising from the posterior surface of the left clavicular head Figures  and 3. DA specialist shoulder surgeon was consulted on the possibility of surgical resection of the osteophytic prominence to relieve the obstruction. The expert orthopaedic opinion was that resection of the entire medial segment of clavicle was the only available course of treatment. This procedure would necessarily result in a significant functional deficit for the patient where previously none existed. The decision was therefore made to treat medically with anticoagulation and ongoing review. The patient remains symptom-free 6 months after the initial event.Effort thrombosis or Paget-Schroetter Syndrome is a form of upper limb DVT that occurs when strenuous activity of the upper limb results in subclavian vein endothelial microtrauma and activation of the coagulation cascade . AnatomiDegenerative osteoarthritis of the sternoclavicular joint is a relatively common condition, especially in the elderly population , with osThis anatomical variant presents diagnostic and therapeutic challenges. The presence and impact of the osteophytic projection could not be fully appreciated on initial presentation as extensive thrombus in the vasculature rendered visualisation of the course and calibre of the subclavian vein difficult on CT imaging. The significance of the osteophytic projection and the severe compression it imparted on the subclavian vein could only be appreciated after surgical intervention and placement of the radiolucent stent.The management of this condition, once identified, is challenging. The accepted treatment for sternoclavicular arthrosis causing significant pain or functional impairment is surgical resection of the medial clavicular head, as less invasive treatment is unlikely to be effective , 10. In Paget-Schroetter syndrome is common in younger active patient groups. When occurring in more elderly patients other aetiologies such as abnormal anatomical compression of the subclavian vein should be considered. As seen in this case, degenerative osteoarthritis with osteophytic development can significantly compress posterior structures and may not be appreciated until the full course of the subclavian vein is possible to be visualized.