Facilitators and barriers to infant post-natal HIV prophylaxis, a qualitative sub-study of the PROMISE-EPI trial in Lusaka, Zambia.
Infant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother's viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention. Individual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis. More barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers' adherence to their own antiretroviral therapy. Accompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries.


Prepubertal and postpubertal vitiligo: a multivariate comparative study in 375 patients.
The onset of vitiligo during childhood is common. Limited data exist that compare the clinical associations of prepubertal and postpubertal vitiligo in Arabs. To compare the clinical profile of pre and postpubertal onset vitiligo. A cross-sectional observational study was conducted. The Vitiligo European Task Force questionnaire was completed for each patient. A total of 375 patients were included; 199 had postpubertal vitiligo (>12 years), and 176 had prepubertal onset vitiligo (<12years). There were more females in the prepubertal group (49%) than in the postpubertal group (29%), p-value <0.001. The prepubertal group has had more involvement than the postpubertal group (45% vs 30%, p=0.004). Only 8 cases of segmental vitiligo were observed; five were observed in the prepubertal group of patients. Female gender (OR=2.3; 95% CI:1.5, 3.5), presence of halo nevus (OR=2.2; 95% CI:1.1, 4.4) and face involvement (OR=1.9; 95% CI:1.2, 2.9) were positively associated with prepubertal vitiligo. Stress, as an onset factor, was positively associated (OR=0.51; 95% CI:0.3, 0.8) with postpubertal onset vitiligo. A possible selection bias toward more severe vitiligo cases can be a limitation, because the study was conducted in a clinic specialized in vitiligo. Moreover, a likelihood of false recall bias cannot be excluded. Our data present clinical evidence that vitiligo behaves mostly the same way in the prepubertal group as in the postpubertal group. However, female over-representation, more face involvement and more halo nevi were observed in prepubertal vitiligo, while stress was more prevalent as an aggravating factor in postpubertal vitiligo patients.


Development of a fluorescence based flux sensor for thin film growth and nanoparticle deposition.
An optical flux sensor, based on the fluorescence properties of materials and nanoparticles, has been developed to control the deposition rate in thin film deposition systems. Using a simple diode laser and a photomultiplier tube with a light filter, we report the detection of gallium atoms and CdSe-ZnS quantum dots. This setup has a high sensitivity and reproducibility.


Detection of mental stress due to oral academic examination via ultra-short-term HRV analysis.
Mental stress may cause cognitive dysfunctions, cardiovascular disorders and depression. Mental stress detection via short-term Heart Rate Variability (HRV) analysis has been widely explored in the last years, while ultra-short term (less than 5 minutes) HRV has been not. This study aims to detect mental stress using linear and non-linear HRV features extracted from 3 minutes ECG excerpts recorded from 42 university students, during oral examination (stress) and at rest after a vacation. HRV features were then extracted and analyzed according to the literature using validated software tools. Statistical and data mining analysis were then performed on the extracted HRV features. The best performing machine learning method was the C4.5 tree algorithm, which discriminated between stress and rest with sensitivity, specificity and accuracy rate of 78%, 80% and 79% respectively.


Hyperuricemia and Its Association With the Severity and Complications of Congestive Heart Failure: A Systematic Review.
Several studies have shown that an association exists between hyperuricemia and heart failure. Despite several innovative management strategies, heart failure is a significant cause of mortality worldwide. Hyperuricemia in heart failure patients leads to poorer outcomes. Additionally, hyperuricemia can be a strong surrogate marker for increased oxidative stress in heart failure patients. This oxidative stress leads to vascular endothelial damage and is linked to worsening heart failure and subsequent mortality. Hence, the measurement of serum uric acid levels in these patients can predict the present and future risk of complications of heart failure. Despite this knowledge, serum uric acid levels are not usually followed up in heart failure patients. This systematic review aims to give additional clarity to this association. We used research from the last twenty years (2002 to 2022) obtained from databases such as PubMed, PubMed Central (PMC), Google Scholar, and Science Direct. We used the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guidelines. We removed duplicates, screened articles on the basis of title and abstract, applied eligibility criteria, and performed quality appraisal. Eventually, 15 articles were selected for review. There were 12 observational studies, two randomized controlled trials, and one meta-analysis. Our review showed that serum uric acid elevation is associated with the severity and complications of congestive heart failure. Serum uric acid can serve as a useful surrogate marker of oxidative stress in congestive heart failure (CHF) patients. The role of xanthine oxidase inhibitors needs to be evaluated further in CHF patients.


Anatomical Effects of Axillary Nodes Dissection on Rat Lymphatic System Model: Indocyanine Green Mapping and Dissection.
Axillary nodes dissection (AND) is an important risk factor for the appearance of breast cancer-related lymphedema (BCRL). The anatomy and pathophysiology leading to the development of BCRL after AND are not completely understood. Despite the existence of lymphedema models after AND, none of them were able to create lymphedemas without additional chemical inflammatory drugs or auxiliary physical techniques (radiotherapy). In this study, we aimed to describe the anatomical changes of AND on a rat's front leg before and after a new surgery technique. AND was performed on seven Wistar rats with a new, posterior surgical approach. Indocyanine green mapping was done before and after surgery to detect "normal and secondary superficial lymphatic pathways" of the operated rat's front legs. Twelve months after surgery, dissections were performed. Subcutaneous blue dye injection of the hand was used to observe superficial and deep lymphatic pathways. Postsurgery, an acute edema of arm and shoulder appeared and persisted for 14-21 days. However, none of the rats showed a chronic secondary lymphedema. In two cases, seromas also appeared. All rats showed substitution functional lymphatic pathways as perforating lymph vessels around the surgical sites. This is the first description of perforating lymph vessels as lymphatic substitution pathways after AND on rats. These results help to understand why a chronic secondary lymphedema could not be created in rats after AND without additional chemical or physical interventions.


A Journey toward Sulfolane Microemulsions Suggested as Inert, Nonaqueous Reaction Media.
Recently, it turned out that nanostructured reaction media containing highly inert solvents as tetrahydrothiophen-1,1-dioxide (sulfolane) are beneficial for strongly oxidizing or reductive reactions. Because of their ability of solubilizing polar and nonpolar solvents with a large nanostructured interface in particular microemulsions provide such interesting reaction media. Starting from the pseudoternary microemulsion H2O-n-octane-C12E4/C12E5 (polyoxyethylene n-alkyl ether), water was successively replaced by the highly inert tetrahydrothiophen-1,1-dioxide (sulfolane). We found that an increasing sulfolane content drives the system beyond the tricritical point. Replacing the already long chain surfactants C12E4 and C12E5 by a mixture of the even longer chain surfactants C18E6 and C18E8, we were able to prepare nonaqueous sulfolane microemulsions for the first time. We also teach how in a second step the phase behavior of the hydrophilic sulfolane-n-octane-C18E8 system can be tuned at constant temperature (as required by the reaction conditions) by addition of the hydrophobic cosurfactant 1-octanol (C8E0). The change in curvature that occurs by adding 1-octanol is demonstrated measuring the size of reverse micelles by DLS. We found that the radius varies from at least 8 to 16 nm, a suitable sizes for inverse nanoreaction vessels.


Delayed Diagnosis of Pharyngeal Perforation following Exploding Tyre Blast Barotrauma.
Introduction. Pharyngoesophageal perforation secondary to barotrauma is a rare phenomenon that can have serious complications if identified late. It is challenging to detect due to nonspecific symptoms. We present a case in which detection proved difficult leading to delayed diagnosis. Case Report. A 27-year-old mechanic presented with haemoptysis, dysphonia, and odynophagia after a car tyre exploded in his face. Flexible nasoendoscopy (FNE) revealed blood in the pharynx, thought to represent mucosal haemorrhage. Initial treatment consisted of IV dexamethasone and antibiotics. After 3 days, odynophagia persisted prompting a CT scan. This revealed a defect in the posterior hypopharynx and surgical emphysema in the deep neck tissues. Contrast swallow confirmed posterior hypopharyngeal leak. NG feeding was commenced until repeated contrast swallow confirmed resolution of the defect. Discussion. Prompt nonsurgical management of pharyngoesophageal perforation has good outcomes but untreated perforation can have serious complications. FNE should be performed routinely, but only a contrast swallow can diagnose a functional perforation. Clinicians should have a high index of clinical suspicion when patients present with barotrauma and odynophagia. Patients should be kept nil by mouth until perforation has been excluded. Conclusion. When faced with cases of facial barotrauma, clinicians should have a low threshold for further imaging to exclude pharyngoesophageal perforation.


Development and validation of a predictive model for in-hospital mortality in patients with sepsis-associated liver injury.
Sepsis is often accompanied by organ dysfunction and acute organ failure, among which the liver is commonly involved. Sepsis patients suffering from liver injury have a greater risk of mortality than patients suffering from general sepsis. As of now, there are no tools that are specifically designed for assessing the prognosis of such patients. This study aimed to develop and validate a model to predict the risk of in-hospital mortality in patients with sepsis-associated liver injury (SALI). Data were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. In the analysis, all patients with SALI who met the inclusion and exclusion criteria were included. A primary outcome was in-hospital mortality, and clinical data were extracted for these patients. In a ratio of 8:2, the data were divided into training and validation groups at random. Least absolute shrinkage and selection operator (LASSO) regression was used for data dimension reduction and feature selection, and independent factors related to prognosis were identified through multi-factor logistics analysis. A nomogram was developed to visualize the model, and the performance of the model was evaluated by the area under the curve (AUC) as well as calibration and decision curve analysis (DCA) through internal verification. A total of 616 and 154 patients with SALI were included in the training and validation cohorts, respectively. The LASSO regression and logistic multivariate analysis showed that nine factors were associated with in-hospital mortality in patients with SALI. Both the training and validation cohorts had higher AUCs than sequential organ failure assessment (SOFA) and simplified acute physiology score 2 (SAPS2): 0.753 (95% CI: 0.715-0.791) and 0.783 (95% CI: 0.749-0.817), respectively. Both the training and validation cohorts showed good calibration results for the prediction model. In terms of clinical practicability, DCA of the predictive model demonstrated greater net benefits than the SOFA and SAPS2 scores. We developed a predictive model that can effectively predict the in-hospital mortality of SALI patients, with satisfactory performance and clinical practicability. This model can assist clinicians in the early identification of high-risk patients and provide a reference for clinical treatment strategies.


Osseous autografts. II. Histological responses to osseous coagulum-bone blend grafts.
Three human intraosseous lesions were treated using osseous coagulum-bone blend as graft material. These sites were surgically removed 6 to 13 weeks after treatment and the blocks prepared for histologic analysis. Periodontal remodeling at the site of grafting was noted in all specimens. This remodeling involved the osseous walls, periodontal ligament, cementum and graft spicules. Both osteoclastic and osteoblastic activities were seen at the borders of the spicules. Exfoliation of spicules was particularly frequent in the six-week specimen. Nevertheless, regenerating of both bone and cementum was actively taking place even in this early specimen and was still evident in the older specimens. Of particular interest was the apparent marked increase in cementogenesis at the graft sites and the variations in parallel or functional orientation of the periodontal ligament in these areas. Significant functional orientation of segments of the periodontal ligament were seenin the early specimens, but not in the latter one. The reason for such variations in ligament pattern is not known at this time.


Automatic breast carcinoma detection in histopathological micrographs based on Single Shot Multibox Detector.
A diagnosis with histological classification by pathologists is very important for appropriate treatments to improve the prognosis of patients with breast cancer. However, the number of pathologists is limited, and assisting the pathological diagnosis by artificial intelligence becomes very important. Here, we presented an automatic breast lesions detection model using microscopic histopathological images based on a Single Shot Multibox Detector (SSD) for the first time and evaluated its significance in assisting the diagnosis. We built the data set and trained the SSD model with 1361 microscopic images and evaluated using 315 images. Pathologists and medical students diagnosed the images with or without the assistance of the model to investigate the significance of our model in assisting the diagnosis. The model achieved 88.3% and 90.5% diagnostic accuracies in 3-class (benign, non-invasive carcinoma, or invasive carcinoma) or 2-class (benign or malignant) classification tasks, respectively, and the mean intersection over union was 0.59. Medical students achieved a remarkably higher diagnostic accuracy score (average 84.7%) with the assistance of the model compared to those without assistance (average 67.4%). Some people diagnosed images in a short time using the assistance of the model (shorten by average 6.4 min) while others required a longer time (extended by 7.2 min). We presented the automatic breast lesions detection method at high speed using histopathological micrographs. The present system may conveniently support the histological diagnosis by pathologists in laboratories.


Hematophagic histiocytosis. A report of 23 new patients and a review of the literature.
The clinical and laboratory features of 23 new patients as well as 50 previously reported patients with the syndrome of hematophagic histiocytosis are reviewed. The syndrome occurs more often in men than women but has no age predilection. Common presenting features include fever, hepatic and splenic enlargement, lymphadenopathy, and profound depression of blood counts. The clinical course is generally fulminant and may be complicated by coagulation abnormalities, hepatic dysfunction and renal failure. In the majority of patients, however, the syndrome is self-limited with resolution of the clinical and laboratory abnormalities within several weeks. Hematophagic histiocytosis generally occurs in patients who develop infections in the setting of preexisting immunologic abnormalities or neoplasms. Viral infections are most commonly involved, but virtually any other infectious agent can precipitate this syndrome. The characteristic morphologic feature of the hematophagic histiocytosis is the proliferation of mature histiocytes actively ingesting other blood cells. These hematophagic histiocytes most commonly involve the bone marrow but may also be present in the lymph nodes, spleen and liver. Other bone marrow abnormalities include hypocellularity with preservation of megakaryocytes, and myelofibrosis. The principal features of this syndrome that distinguish it from malignant histiocytosis are the cytologic maturity and degree of hematophagic activity of the histiocytes as well as its more favorable prognosis. In some patients, however, a clear distinction of malignant from reactive histiocytosis will not be possible until a clonal marker for malignant histiocytes is identified. Based in our experience, the syndrome of hematophagic histiocytosis appears to be more common than malignant histiocytosis.


Evidence for the clinical association between Demodex and rosacea:a review.
Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes. Rosacea appears to have a close bond with Demodex. Recent studies have implicated that Demodex mites are involved in the development of rosacea. Based on a comprehensive review of the current literature, we have cited substantial evidence supporting this relationship, proposed a possible vicious cycle between Demodex and rosacea, and illustrated the changes in immune responses during this process. In addition, we recommend that patients with both rosacea and Demodex infection be treated early with a combination of topical ivermectin and topical Th1 inhibitors to improve treatment outcomes.


Sample preparation prior to the LC-MS-based metabolomics/metabonomics of blood-derived samples.
Blood represents a very important biological fluid and has been the target of continuous and extensive research for diagnostic, or health and drug monitoring reasons. Recently, metabonomics/metabolomics have emerged as a new and promising 'omics' platform that shows potential in biomarker discovery, especially in areas such as disease diagnosis, assessment of drug efficacy or toxicity. Blood is collected in various establishments in conditions that are not standardized. Next, the samples are prepared and analyzed using different methodologies or tools. When targeted analysis of key molecules (e.g., a drug or its metabolite[s]) is the aim, enforcement of certain measures or additional analyses may correct and harmonize these discrepancies. In omics fields such as those performed by holistic analytical approaches, no such rules or tools are available. As a result, comparison or correlation of results or data fusion becomes impractical. However, it becomes evident that such obstacles should be overcome in the near future to allow for large-scale studies that involve the assaying of samples from hundreds of individuals. In this case the effect of sample handling and preparation becomes very serious, in order to avoid wasting months of work from experts and expensive instrument time. The present review aims to cover the different methodologies applied to the pretreatment of blood prior to LC-MS metabolomic/metabonomic studies. The article tries to critically compare the methods and highlight issues that need to be addressed.


Yellow and green pigments from Calophyllum inophyllum L. seed oil induce cell death in colon and lung cancer cells.
Natural compounds have been candidates for anticancer medicine over the last 20 years. During the process of isolating seed oil from Calophyllum inophyllum L., yellow and green pigments containing multiple compounds with an aromatic structure were identified. High-performance liquid chromatography and nuclear magnetic resonance analysis of these pigments revealed that the compounds present were identical, but the concentration of the compounds was different. Treatment with the pigments was able to induce the death of DLD-1 human colon cancer cells and increase the percentage of the cells in the sub-G1 and sub-G2/M phases in a dose-dependent manner. Additionally, the pigments were able to exhibit cytotoxic activity on A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines at 24 h, with half-maximal inhibitory concentrations (IC50) values of 0.1206 and 0.0676%, respectively for green pigments, and 0.0434 and 0.0501%, respectively for yellow pigments. Furthermore, a decrease in IC50 value was associated with an increase in the duration of treatment. However, a sharp decrease in IC50 value of the yellow pigment was observed for H1975 cells at 48 h and for A549 cells at 72 h compared with no change in IC50 value for the green pigment with time, suggesting that the pigments function and induce cell death differently in the two cell lines. An investigation was performed into the synergistic effect of the green pigment and gefitinib (Iressa®, ZD1839), which is a selective epidermal growth factor receptor-tyrosine kinase inhibitor to block growth factor-mediated cell proliferation. The combination of the green pigment and gefitinib resulted in an enhancement of the decrease in viability of A549 and H1975 cells compared with treatment with gefitinib alone, which suggested that treatment with the green pigments was able to enhance the sensitivity of NSCLC cells to gefitinib. In conclusion, these pigments may be considered for development as anti-colon cancer agents.


Measurement of sub-nanonewton forces inside a scanning electron microscope.
van der Waals forces, electrostatic interactions, and capillary forces are the dominant force interactions at the micro- and nanoscale. This complex ensemble of surface forces is oftentimes summarized as adhesion and is important for various applications and research fields. So far, numerous measurement techniques have evolved in this field. However, there is still a lack of experimental insight into the complex interplay of van der Waals, electrostatic, and capillary forces for small force ranges below 10 nN, as this is the order of magnitude of the latter, which can shadow other interactions in ambient and even inert gas environments. To exclude capillary forces and thus to turn the van der Waals and electrostatic forces into the most significant interactions, we develop an interferometric force spectroscopy setup based on a scanning probe technique, featuring a sub-nanonewton resolution, and integrate it into the vacuum chamber of a scanning electron microscope. In this work, we describe the setup integration, show the long-term drift behavior and resolution capabilities, and conduct first measurements of adhesion energies between a silica colloidal probe and a silicon substrate. The presented setup shows its capability to reliably measure adhesive interactions in vacuum and an ambient environment with a sub-nanonewton resolution proving its potential to allow for the investigation of the separate contribution of capillary, van der Waals, and electrostatic interactions to adhesion and for a systematic experimental validation of the established adhesion theories and approximations on the micro- and nanoscale.


A de novo variant in the ASPRV1 gene in a dog with ichthyosis.
Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding "aspartic peptidase, retroviral-like 1", which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.


Endothelial cells reestablish functional integrity after reversible permeabilization.
Permeabilization is an important tool in cell biology that allows manipulation of intracellular mechanisms by introduction of probes and regulatory molecules into the cell cytoplasm. We found that incubation of endothelial cells (ECs) with glass beads resulted in nonspecific permeabilization of human and bovine ECs without removal of the cells from monolayer culture. This poration of the plasma membrane allowed the introduction of macromolecules (dextrans less than or equal to 152 kd and immunoglobulins) as well as small, charged molecules (Lucifer Yellow). We found that nonspecific permeabilization of the EC was transient and defined the conditions under which integrity of the plasma membrane was reestablished. This process was dependent on time, temperature, and the presence of extracellular calcium. We also demonstrated that permeabilized ECs regain functional characteristics. This was defined by a number of criteria, including the ability to rapidly reestablish confluent monolayer morphology, to extrude Lucifer Yellow, to adhere and spread after passage, and to synthesize biologically active molecules after stimulation with a receptor-mediated agonist. Thus, transiently porated ECs loaded with appropriate probes can be used in studies of regulatory mechanisms while remaining in monolayer culture, a condition in which many phenotypic features are similar to in situ endothelium. Furthermore, the porated EC may be a useful model for defining the mechanisms that influence the repair of endothelial plasma membrane injury.


Current advances in the development of novel polymeric nanoparticles for the treatment of neurodegenerative diseases.
Effective intervention is essential to combat the coming epidemic of neurodegenerative (ND) diseases. Nanomedicine can overcome restrictions of CNS delivery imposed by the blood-brain barrier, and thus be instrumental in preclinical discovery and therapeutic intervention of ND diseases. Polymeric nanoparticles (PNPs) have shown great potential and versatility to encapsulate several compounds simultaneously in controlled drug-delivery systems and target them to the deepest brain regions. Here, we critically review recent advances in the development of drugs incorporated into PNPs and summarize the molecular changes and functional effects achieved in preclinical models of the most common ND disorders. We also briefly discuss the many challenges remaining to translate these findings and technological advances successfully to current clinical settings.


Effects of a low-carbohydrate-high-protein pre-exercise meal in type 1 diabetes - a randomised, crossover trial.
Current guidelines for exercise-related glucose management focus on reducing bolus and/or basal insulin doses and considering carbohydrate intake. Yet far less attention has been paid to the potential role of other macronutrients alongside carbohydrates on glucose dynamics around exercise. To investigate the effects of a low-carbohydrate-high-protein (LCHP) compared to a high-carbohydrate-low-protein (HCLP) pre-exercise meal on the metabolic, hormonal, and physiological responses to exercise in adults with insulin pump-treated type 1 diabetes. Fourteen adults with insulin pump-treated type 1 diabetes (11 females with a median [range] HbA1c of 50 [43-59] mmol/mol (6.7 [6.1-7.5] %), age of 49 [25-65] years, and BMI of 24.0 [19.3-27.1] kg/m2) completed an unblinded, two-arm, randomised, crossover study. Participants ingested isocaloric meals that were either LCHP (carbohydrate 21%, protein 52%, fat 27%) or HCLP (carbohydrate 52%, protein 21%, fat 27%) 90 min prior to undertaking 45 min of cycling at moderate intensity. Meal insulin bolus was dosed according to meal carbohydrate content but reduced by 25%. Basal insulin rates were reduced by 35% from meal ingestion to end of exercise. Around exercise the coefficient of variability was lower during LCHP (LCHP:14.5±5.3 vs. HCLP: 24.9±7.7%, p=0.001). Over exercise, LCHP was associated with a lesser drop (LCHP: Δ-1.49±1.89 vs. HCLP: Δ-3.78±1.95 mmol/L, p=0.001). Mean insulin concentration was 30% lower during exercise for LCHP compared to HCLP (LCHP: 25.5±11.0 vs. HCLP: 36.5±15.9 mU/L, p<0.001). Ingesting a LCHP pre-exercise meal lowered plasma glucose variability around exercise and diminished the drop in plasma glucose over exercise.


Intellectual disability complicated by sexual addiction: an uncommon presentation of a common condition.
A young man presented with high libido for 3 years, associated with preoccupation with sexual thoughts combined with his pursuit of pornographic materials. He had strong psychological cravings for and had spent large amount of money on sex, resulting in a dispute with his family. There were no mood or psychotic symptoms. Medical history revealed recent diagnosis of gonococcal urethritis. Cognitive assessment showed subtle deficiencies in reasoning and executive functions. There was occasional use of alcohol. Sexual addiction with comorbid mild intellectual disability was diagnosed, and pharmacological as well as psychological management were started.


Biochar-Mediated Degradation of Roxarsone by Shewanella oneidensis MR-1.
It is widely believed that biochar plays an essential role in sequestrating pollutants. The impacts of biochar on microbial growth, and consequently on the environmental fate of pollutants, however, remains poorly understood. In this study, wheat-straw-derived biochar was used to investigate how biochar amendment affected Shewanella oneidensis MR-1 growth and roxarsone transformation in water under anaerobic conditions. Three biochar with different physicochemical properties were used to mediate the roxarsone degradation. The results showed that the degradation rate of roxarsone could be accelerated by the increase of biochar pyrolysis temperature. From the characterization of biochar, the total specific surface area, micropore surface area and micropore volume of biochar increase, but the average pore diameter decreases as the pyrolysis temperature increases. Through infrared spectroscopy analysis, it was found that as the pyrolysis temperature increases, the degree of condensation of biochar increases, thereby increasing the pollutant removal rate. From the changes of the relative concentration of MR-1 and its secreted extracellular polymer content, the growth promotion ability of biochar also increases as the pyrolysis temperature increases. These results suggest that wheat-straw-derived biochar may be an important agent for activating microbial growth and can be used to accelerate the transformation of roxarsone, which could be a novel strategy for roxarsone remediation.


Estimating conductive sapwood area in diffuse and ring porous trees with electronic resistance tomography.
Accurately estimating sapwood area is essential for modelling whole-tree or stand-scale transpiration from point-flow sap-flux observations. In this study, we tested the validity of electrical resistance tomography (ERT) to locate the sapwood-heartwood (SW/HW) interface for two ring porous (Quercus nigra L. and Quercus virginiana Mill.) and one diffuse porous (Acer rubrum L.) species. Estimates derived from the ERT analyses were compared with the SW/HW interface measured following dye perfusion testing. The ERT results revealed spatial variation in electrical resistance, with higher resistivity in the inner part of the cross sections. Regression analyses showed that ERT was able to accurately account for 97% and 80% of the variation in sapwood area (calculated as R2) for Q. virginiana (n = 19) and Q. nigra (n = 7), respectively, and 56% of the variation in the diffuse porous species (n = 8). Root mean square error (RMSE) values for sapwood areas of the ring porous species were 11.12 cm2 (19%) and 25.98 cm2 (33%) for Q. virginiana and Q. nigra, respectively. Sapwood area estimates for diffuse wood carried greater error (RMSE = 33.52 cm2 (131%)). Model bias for all sapwood area estimates was negative, suggesting that ERT had a tendency to overestimate sapwood areas. Electrical resistance tomography proved to be a significant predictor of sapwood area in the three investigated species, although it was more reliable for ring porous wood. In addition to the results, a comprehensive code sequence for use with R statistical software is provided, so that other investigators may follow the same method.