Skin models of cutaneous toxicity, transdermal transport and wound repair.

Skin is widely used as a drug delivery route due to its easy access and the possibility of using relatively painless methods for the administration of bioactive molecules. However, the barrier properties of the skin, along with its multilayer structure, impose severe restrictions on drug transport and bioavailability. Thus, bioengineered models aimed at emulating the skin have been developed not only for optimizing the transdermal transport of different drugs and testing the safety and toxicity of substances but also for understanding the biological processes behind skin wounds. Even though in vivo research is often preferred to study biological processes involving the skin, in vitro and ex vivo strategies have been gaining increasing relevance in recent years. Indeed, there is a noticeably increasing adoption of in vitro and ex vivo methods by internationally accepted guidelines. Furthermore, microfluidic organ-on-a-chip devices are nowadays emerging as valuable tools for functional and behavioural skin emulation. Challenges in miniaturization, automation and reliability still need to be addressed in order to create skin models that can predict skin behaviour in a robust, high-throughput manner, while being compliant with regulatory issues, standards and guidelines. In this review, skin models for transdermal transport, wound repair and cutaneous toxicity will be discussed with a focus on high-throughput strategies. Novel microfluidic strategies driven by advancements in microfabrication technologies will also be revised as a way to improve the efficiency of existing models, both in terms of complexity and throughput.

Advances in Environmentally Friendly Techniques and Circular Economy Approaches for Insect Infestation Management in Stored Rice Grains.

Rice (Oryza sativa L.) is a staple food for about half of the world's population. Therefore, it is important to search for solutions that minimise losses and production costs for producers and ensure food quality and safety for consumers. Improved methods for the detection and monitoring of hidden infestations are useful for adopting infestation control measures. Chemical methods are used to prevent rice losses due to infestations; changing this situation, however, is of the utmost importance, as it harms the environment and human health. The management of infestation by controlled storage conditions, namely temperature and atmosphere composition and the use of current fossil-based packaging with modified atmospheres, is well recognised. The use of environmentally friendly solutions is promising, but it is necessary to perform a life-cycle assessment and cost analysis to evaluate their effectiveness. According to the principles of circular economy, the integration of the best-selected treatments/solutions for insect management, along with the use of biopackaging from rice by-products are recommended. This review describes the methods of detection and control of infestation as well as several promising alternatives to chemical treatments; however, more research is needed in order to obtain effective technological solutions that can be applied at an industrial scale.

Predicting Prognosis in Internal Medicine: A Short and Long-Term Mortality Comparison Analysis.

Introduction The marked increase in life expectancy seen in Portugal in the last five decades led to a change in the profile of patients being most commonly admitted in internal medicine wards. In deciding the best care for these patients, prognostication models are needed in order to reduce readmissions, mortality, and adequate care. We aimed to study short and long-term mortality and predictors of all-cause mortality, independently of cause admission, of patients admitted in an internal medicine ward. Methods This two-part, single-center study enrolled patients from October 2013 to October 2014 with a follow-up of 60 months. Results A total of 681 patients were included; the mean age was 75.86 years with 60.4% females. The most frequent comorbidities were anemia, hypertension, and renal impairment. More than half of the population died in the follow-up period (51.5%). Deaths were significantly higher in the first six months after discharge (53% of all deaths) and then decreased abruptly to 11.6% in the second half-year after discharge. Based on the multivariate logistic regression model, with age over 80 years, anemia and neoplasm were independent predictors of short-term (p<0.001, p=0.001, p<0.001, respectively) and long-term (p<0.001 for the three conditions) mortality. Heart failure (p=0.018) and diabetes (p=0.025) were also predictors of long-term mortality. Conclusion High mortality, mainly in the first six months after discharge, elicits strategies targeting transition of care and close follow-up in the first months, which can be the key to improving outcomes. Identification of patients at higher risk may help design realistic models aiming to improve care for this frail population and decrease morbimortality.

Improving the Nutritional, Structural, and Sensory Properties of Gluten-Free Bread with Different Species of Microalgae.

Microalgae are an enormous source of nutrients that can be utilized to enrich common food of inherently low nutritional value, such as gluten-free (GF) bread. Addition of the algae species: Tetraselmis chuii (Tc), Chlorella vulgaris (Cv), and Nannochloropsis gaditana (Ng) biomass led to a significant increase in proteins, lipids, minerals (Ca, Mg, K, P, S, Fe, Cu, Zn, Mn), and antioxidant activity. Although, a compromise on dough rheology and consequential sensory properties was observed. To address this, ethanol treatment of the biomass was necessary to eliminate pigments and odor compounds, which resulted in the bread receiving a similar score as the control during sensory trials. Ethanol treatment also resulted in increased dough strength depicted by creep/recovery tests. Due to the stronger dough structure, more air bubbles were trapped in the dough resulting in softer breads (23-65%) of high volume (12-27%) vs. the native algae biomass bread. Breads baked with Ng and Cv resulted in higher protein-enrichment than the Tc, while Tc enrichment led to an elevated mineral content, especially the Ca, which was six times higher than the other algae species. Overall, Ng, in combination with ethanol treatment, yielded a highly nutritious bread of improved technological and sensory properties, indicating that this species might be a candidate for functional GF bread development.

Can increased load carriage affect lower limbs kinematics during military gait?

The aim of this study was to investigate if increased load carriage, in male military personnel, can affect the lower limbs kinematics. Twelve male military volunteers from the Portuguese Army were recruited and evaluated in an unloaded and loaded gait condition. Linear kinematics and lower limbs joint angle at heel strike, midstance and toe off were calculated. The stance, swing and double support times were found to be different between load conditions (p < 0.05). There was an interaction between load and limb (p < 0.05) for joint angles, during midstance, with limbs performing different movements in the frontal plane during loaded gait. Load increase had a different effect on the right knee, with a reduction in the abduction (valgus). This study may be beneficial in offering suggestion to improve the performance of gait with load and in an attempt to help prevent possible injuries. Practitioner summary: Increased load can affect lower limbs of male soldiers at the pelvic, hip and knee angles on the frontal plane, which can alter the joint force distribution. While these alterations may indicate protective mechanics, load management procedures should be implemented along with gait monitoring to avoid negative effects in performance.

Palliative Care in Heart Failure: Challenging Prognostication.

Heart failure (HF) is a chronic progressive disease with high morbimortality and poor quality of life (QoL). Palliative care significantly improves clinical outcomes but few patients receive it, in part due to challenging decisions about prognosis. This retrospective study, included all patients consecutively discharged from an Acute Heart Failure Unit over a period of one year, aiming to assess the accuracy of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in predicting mortality. Additionally, predictors of death at one and three years were explored using a multivariate regression model. The MAGGIC score was useful in predicting mortality, without significant difference between mortality observed at three-years follow-up compared with a mortality given by the score (p=0.115). Selected variables were statistically compared showing that poor functional status, high New York Heart Association (NYHA) at discharge, psychopharmacs use, and high creatininemia were associated with higher mortality (p<0.05). The multivariate regression model identified three predictors of one-year mortality: psychopharmacs baseline use (OR=4.110; p=0.014), angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEI/ARB) medication at discharge (OR=0.297; p=0.033), and higher admission's creatinine (OR=2.473; p=0.028). For three-year mortality outcome, two variables were strong independent predictors: psychopharmacs (OR=3.330; p=0.022) and medication with ACEI/ARB at discharge (OR=0.285; p=0.018). Models' adjustment was assessed through the receiver operating characteristic (ROC) curve. The best model was the one-year mortality (area under the curve, AUC 81%), corresponding to a good discrimination power. Despite prognostication, when setting goals of care an individualised patient-centred approach is imperative, based on the patient's objectives and needs. Risk factors related to poorer outcomes should be considered, in particular, higher NYHA at discharge which also represents symptom burden. Hospitalisation is an opportunity to optimize global care for heart failure patients including palliative care.

Pain in an Internal Medicine Ward: An Undervalued Reality?

Introduction Pain is prevalent in most pathologic situations that require healthcare and is very common in hospitalised patients. However, there is limited evidence about the prevalence and the actual management of pain in medical wards. The aim of this work was to evaluate and characterise pain management in an internal medicine ward. Methods Retrospective analysis of clinical data of patients consecutively discharged from the internal medicine ward of a central tertiary hospital over a period of five months in 2018. Results 199 patients evaluated, the median age was 78 years and 63% were female. Of these, 14% had a previous diagnosis of chronic pain, 24% were on chronic pain medication, and in 29% medication was interrupted. Pain was noted in medical records of 118 patients, with moderate to severe intensity in 67%. Among those, 71% had pain occurrence registered in the medical notes but not characterised in duration in 61%. The most common attributed etiologies of pain were musculoskeletal (16%), visceral (9%), and headache (8%); no identifiable cause was specified in 57%. In the group of patients reporting pain, 63% received analgesics. Opioids were used in 35% and 47% of patients with moderate and severe pain, respectively. At discharge, 12 patients were still referred pain, 16 had pain listed as a diagnosis, 45 were medicated for pain, and eight were referred for pain consultation. Conclusions Despite being highly prevalent in the internal medicine ward, pain is still under-recognised, undervalued, and under-treated. Education of healthcare staff and adoption of treatment protocols is essential to improve care for these patients.

Epidural Abscess: A Cause of Back Pain That Must Not Be Missed.

Low back and cervical pain are common emergency department complaints. Most cases represent low-risk pathologies but in rare cases, it can be a symptom of a serious underlying disease and the distinction can be challenging. A case is reported of a 58-year-old male with recurrent cervical pain requiring several emergency department visits. He eventually presented with intense cervical and low back pain, tetraparesis, and dyspnea. His condition deteriorated in less than 24 hours, evolving with fever, shock, and respiratory insufficiency and was admitted to the Intensive Care Unit for aminergic support, invasive mechanical ventilation and started on empiric antibiotics. Investigations revealed raised inflammatory markers and a cervical pre-vertebral purulent collection associated with an epidural collection at the level of C2 to C5 with spinal cord compression. The patient underwent transoral drainage and removal of the posterior C1 arch along with C2-C3-C4-C5 laminectomy. Staphylococcus aureus was isolated in the blood, pus, and bone. Re-intervention was required due to persistent pre-vertebral abscesses with clinical improvement thereafter. Eight weeks of antibiotic treatment were completed in total. The patient was discharged after 72 days of hospitalization with significant improvement in force and autonomy. Epidural abscess is a rare finding that can cause rapid irreversible neurological deterioration. Clinical suspicion must be high for an early diagnosis and treatment, essential for a better prognosis.

Leptospirosis, a Re-emerging Threat.

Leptospirosis is a zoonosis transmitted by an animal vector and caused by the spirochete bacteria Leptospira. Human infection is rare and acquired by exposure to environmental sources (animal urine, contaminated water, soil, or infected animal tissue). It can have an extremely broad presentation, ranging from asymptomatic to serious illness. We report the case of a 59-year-old man admitted to the hospital with myalgia, fever, and abdominal discomfort. Routine laboratory tests revealed raised inflammatory markers, thrombocytopenia, kidney dysfunction, and hepatic cytolysis and cholestasis. The hypothesis of zoonosis was raised based on symptoms and analytical changes despite the weak epidemiological history to support it. Although leptospira serology tests were negative on admission, a polymerase chain reaction test was requested due to a high degree of suspicion which came back positive. The patient completed eight days of doxycycline with favorable clinical and analytical progression. This case highlights the changing epidemiology of leptospirosis and the importance of having a high degree of suspicion even outside endemic zones. It also highlights the importance of a wise choice of diagnostic tests according to the disease stage.

A Reflection on the Use of Enoxaparin Based on Three Case Reports.

Enoxaparin is indicated for the treatment or prevention of many clinical disorders including deep vein thromboembolism, atrial fibrillation and mechanical valve thrombosis. It is one of the most commonly prescribed drugs in hospitals. However, haemorrhagic complications can occur, particularly in the elderly, patients with renal function impairment and patients with a very high or very low body weight. The authors describe the cases of three patients who had one or more risk factors for haemorrhagic complications, such as abdominal haematomas. The clinical presentation was similar in all three cases, with sudden-onset abdominal pain, an altered state of consciousness and hypotension. In all cases, investigation showed acute anaemia and large abdominal haematomas on imaging studies. A conservative approach was taken in the three patients, with suspension and reversal of anticoagulation, fluid resuscitation and red blood cell transfusion. Haemodynamic stability was achieved in two of the patients, but the third patient died. The authors consider it is important to present these case reports because of the widespread use of enoxaparin, and the need for rigorous dose adjustment for renal function variations and body weight. We hope this article raises awareness of haemorrhagic complications in high-risk groups and propose protocols are introduced for dose adjustment and monitoring the efficacy of enoxaparin. LEARNING POINTS: Clinicians should consider the possibility of enoxaparin-associated haemorrhagic complications in high-risk groups.Prompt identification and treatment of the haemorrhagic disorder can improve outcome.Correct dosing with anti-Xa in high-risk populations, such as the elderly, those with abnormal renal function and those with extremely high or low body weight, may be helpful in patients anticoagulated with enoxaparin.

Acute Anaemia: A Challenging Diagnosis.

Acute anaemia is characterized by a reduction in the number of red blood cells, haemoglobin levels or haematocrit. By far the most common aetiology is haemorrhage, but in its absence other less frequent causes should be considered. The authors present the case of a 42-year-old man with a diagnosis of glucose-6-phosphate deficiency and progressing gastric signet ring cell carcinoma, who was admitted to the internal medicine department for symptomatic back pain control. During his hospitalization, the patient developed acute anaemia with schistocytes on peripheral blood smear with no concurrent hyperbilirubinaemia or decreased haptoglobin. Bone metastatic disease was documented. The case was revised with the transfusion medicine department and malignancy-associated microangiopathic haemolytic anaemia (Ma-MAHA) was suggested. The patient was transferred to the oncology department and later discharged, dying at home shortly afterwards. LEARNING POINTS: The possibility of multiple aetiologies for anaemia in the same patient should be considered.Pathophysiological mechanisms are important in the differential diagnosis of anaemia.Malignancy-associated microangiopathic haemolytic anaemia can present as a paraneoplastic syndrome.

Simple decision-tree tool to facilitate author identification of reporting guidelines during submission: a before-after study.

BACKGROUND: There is evidence that direct journal endorsement of reporting guidelines can lead to important improvements in the quality and reliability of the published research. However, over the last 20 years, there has been a proliferation of reporting guidelines for different study designs, making it impractical for a journal to explicitly endorse them all. The objective of this study was to investigate whether a decision tree tool made available during the submission process facilitates author identification of the relevant reporting guideline. METHODS: This was a prospective 14-week before-after study across four speciality medical research journals. During the submission process, authors were prompted to follow the relevant reporting guideline from the EQUATOR Network and asked to confirm that they followed the guideline ('before'). After 7 weeks, this prompt was updated to include a direct link to the decision-tree tool and an additional prompt for those authors who stated that 'no guidelines were applicable' ('after'). For each article submitted, the authors' response, what guideline they followed (if any) and what reporting guideline they should have followed (including none relevant) were recorded. RESULTS: Overall, 590 manuscripts were included in this analysis-300 in the before cohort and 290 in the after. There were relevant reporting guidelines for 75% of manuscripts in each group; STROBE was the most commonly applicable reporting guideline, relevant for 35% (n = 106) and 37% (n = 106) of manuscripts, respectively. Use of the tool was associated with an 8.4% improvement in the number of authors correctly identifying the relevant reporting guideline for their study (p < 0.0001), a 14% reduction in the number of authors incorrectly stating that there were no relevant reporting guidelines (p < 0.0001), and a 1.7% reduction in authors choosing a guideline (p = 0.10). However, the 'after' cohort also saw a significant increase in the number of authors stating that there were relevant reporting guidelines for their study, but not specifying which (34 vs 29%; p = 0.04). CONCLUSION: This study suggests that use of a decision-tree tool during submission of a manuscript is associated with improved author identification of the relevant reporting guidelines for their study type; however, the majority of authors still failed to correctly identify the relevant guidelines.