Retinoic acid modulation of granule cell activity and spatial discrimination in the adult hippocampus.

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARß) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

Influence of postprinting cleaning methods on the cleaning efficiency and surface and mechanical properties of three-dimensionally printed resins.

STATEMENT OF PROBLEM: The outcome of photopolymerized 3-dimensional (3D) printing is influenced by the methods used for postprinting cleaning, yet information on postprinting cleaning is sparse. PURPOSE: The purpose of this in vitro study was to assess the cleaning efficiency and surface and mechanical properties of 3D printed resin according to postprinting cleaning methods. MATERIAL AND METHODS: Specimens were fabricated from a 3D model using resin materials (NextDent C&B MFH and DIOnavi-P. MAX) and were tested for postprinting cleaning methods for 5 minutes with isopropyl alcohol, isopropyl alcohol + ultrasonic, ethyl alcohol, ethyl alcohol + ultrasonic, and ultrasonic alone. Postpolymerization was followed for 5 minutes. The cleaning efficiency, microcomputed tomography (µCT), surface roughness, Vickers hardness, and flexural strength of the specimens were evaluated. The 1-way ANOVA test was performed after considering normality. A post hoc analysis with Bonferroni was also performed (α=.008 or.005). RESULTS: Ultrasonic in addition to cleaning solutions significantly improved the cleaning efficiency in NextDent C&B MFH specimens (P<.005), whereas ultrasonic did not affect the efficiency in DIOnavi-P. MAX specimens. No significant differences were found in surface roughness by postprinting cleaning methods in either NextDent C&B MFH or DIOnavi-P. MAX (P>.005). No significant changes in surface hardness were observed by postprinting cleaning methods (P>.008). In the NextDent C&B MFH, ethyl alcohol + ultrasonic significantly decreased the flexural strength (P<.005). There were no significant differences in the flexural strength in the DIOnavi-P. MAX (P>.005). CONCLUSIONS: Ethyl alcohol was comparable with isopropyl alcohol for use as a postprinting cleaning solution for both NextDent C&B MFH and DIOnavi-P. MAX. The addition of ultrasonic to cleaning solutions should be applied with caution. These findings suggest that different postprinting cleaning methods can be recommended depending on the 3D printed resin materials.

Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress.

Fear overgeneralization is a maladaptive response to traumatic stress that is associated with the inability to discriminate between threat and safety contexts, a hallmark feature of post-traumatic stress disorder (PTSD). However, the neural mechanisms underlying this deficit remain unclear. Here, we show that traumatic stress exposure impairs contextual discrimination between threat and safety contexts in the learned helplessness (LH) model. Mossy cells (MCs) in the dorsal hippocampus are suppressed in response to traumatic stress. Bidirectional manipulation of MC activity in the LH model reveals that MC inhibition is causally linked to impaired contextual discrimination. Mechanistically, MC inhibition increases the number of active granule cells in a given context, significantly overlapping context-specific ensembles. Our study demonstrates that maladaptive inhibition of MCs after traumatic stress is a substantial mechanism underlying fear overgeneralization with contextual discrimination deficit, suggesting a potential therapeutic target for cognitive symptoms of PTSD.

Frequency-potency analysis of IgG+ memory B cells delineates neutralizing antibody responses at single-cell resolution.

Identifying individual functional B cell receptors (BCRs) is common, but two-dimensional analysis of B cell frequency versus BCR potency would delineate both quantity and quality of antigen-specific memory B cells. We efficiently determine quantitative BCR neutralizing activities using a single-cell-derived antibody supernatant analysis (SCAN) workflow and develop a frequency-potency algorithm to estimate B cell frequencies at various neutralizing activity or binding affinity cutoffs. In an HIV-1 fusion peptide (FP) immunization study, frequency-potency curves elucidate the quantity and quality of FP-specific immunoglobulin G (IgG)+ memory B cells for different animals, time points, and antibody lineages at single-cell resolution. The BCR neutralizing activities are mainly determined by their affinities to soluble envelope trimer. Frequency analysis definitively demonstrates dominant neutralizing antibody lineages. These findings establish SCAN and frequency-potency analyses as promising approaches for general B cell analysis and monoclonal antibody (mAb) discovery. They also provide specific rationales for HIV-1 FP-directed vaccine optimization.

Identification of Terpene Compositions in the Leaves and Inflorescences of Hybrid Cannabis Species Using Headspace-Gas Chromatography/Mass Spectrometry.

Although cannabidiol and tetrahydrocannabinol in Cannabis species exert their pharmacological effects via the endocannabinoid system, it is believed that other phytochemicals, particularly terpenes, can modulate therapeutic outcomes through the entourage effect. Therefore, to gain a better understanding of the pharmacological effects of Cannabis, obtaining information on phytochemical compositions, including mono-, di-, and sesqui-terpenes in Cannabis species is essential. Applying a sophisticated analytical method is indispensable. In this study, headspace-gas chromatography/mass spectrometry (HS-GC/MS) was employed to identify major terpenes in the leaves and inflorescences of hybrid Cannabis species. The incubation time and temperature conditions for HS-GC/MS were optimized. This method was successfully applied to the leaves (n = 9) and inflorescences (n = 7) of hybrid Cannabis species. A total of 26 terpenes in Cannabis species were detected, and six major components, such as α-pinene (9.8-2270 µg/g), ß-pinene (2.6-930 µg/g), myrcene (0.7-17,400 µg/g), limonene (1.3-300 µg/g), ß-caryophyllene (60-3300 µg/g), and α-humulene (40-870 µg/g), were quantified. Each sample showed different terpene compositions, but six major terpenes among all the terpenes detected were consistently found in both the leaves and inflorescences of hybrid Cannabis species. In this study, the six major terpenes' potential in hybrid Cannabis species was evaluated as biomarkers to distinguish hybrid Cannabis species samples. This study contributes to a better understanding of the entourage effect of Cannabis-based botanical drugs.

Visualizing Hand Force with Wearable Muscle Sensing for Enhanced Mixed Reality Remote Collaboration.

In this paper, we present a prototype system for sharing a user's hand force in mixed reality (MR) remote collaboration on physical tasks, where hand force is estimated using wearable surface electromyography (sEMG) sensor. In a remote collaboration between a worker and an expert, hand activity plays a crucial role. However, the force exerted by the worker's hand has not been extensively investigated. Our sEMG-based system reliably captures the worker's hand force during physical tasks and conveys this information to the expert through hand force visualization, overlaid on the worker's view or on the worker's avatar. A user study was conducted to evaluate the impact of visualizing a worker's hand force on collaboration, employing three distinct visualization methods across two view modes. Our findings demonstrate that sensing and sharing hand force in MR remote collaboration improves the expert's awareness of the worker's task, significantly enhances the expert's perception of the collaborator's hand force and the weight of the interacting object, and promotes a heightened sense of social presence for the expert. Based on the findings, we provide design implications for future mixed reality remote collaboration systems that incorporate hand force sensing and visualization.

Effects of Avatar Transparency on Social Presence in Task-Centric Mixed Reality Remote Collaboration.

Despite the importance of avatar representation on user experience for Mixed Reality (MR) remote collaboration involving various device environments and large amounts of task-related information, studies on how controlling visual parameters for avatars can benefit users in such situations have been scarce. Thus, we conducted a user study comparing the effects of three avatars with different transparency levels (Nontransparent, Semi-transparent, and Near-transparent) on social presence for users in Augmented Reality (AR) and Virtual Reality (VR) during task-centric MR remote collaboration. Results show that avatars with a strong visual presence are not required in situations where accomplishing the collaborative task is prioritized over social interaction. However, AR users preferred more vivid avatars than VR users. Based on our findings, we suggest guidelines on how different levels of avatar transparency should be applied based on the context of the task and device type for MR remote collaboration.

A portable smartphone-based colorimetric sensor that utilizes dual amplification for the on-site detection of airborne bacteria.

Over the past few years, infections caused by airborne pathogens have spread worldwide, infecting several people and becoming an increasingly severe threat to public health. Therefore, there is an urgent need for developing airborne pathogen monitoring technology for use in confined environments to enable epidemic prevention. In this study, we designed a colorimetry-based bacterial detection platform that uses a clustered regularly interspaced short palindromic repeat-associated protein 12a system to amplify signals and a urease enzyme to induce color changes. Furthermore, we have developed a smartphone application that can distinguish colors under different illumination conditions based on the HSV model and detect three types of disease-causing bacteria. Even synthetic oligomers of a few picomoles of concentration and genomic DNA of airborne bacteria smaller than several nanograms can be detected with the naked eye and using color analysis systems. Furthermore, in the air capture model system, the bacterial sample generated approximately a 2-fold signal difference compared with that in the control group. This colorimetric detection method can be widely applied for public safety because it is easy to use and does not require complex equipment.

Conductive Thread-Based Immunosensor for Pandemic Influenza A (H1N1) Virus Detection.

Infectious agents such as viruses pose significant threats to human health, being transmitted via direct contact as well as airborne transmission without direct contact, thus requiring rapid detection to prevent the spread of infectious diseases. In this study, we developed a conductive thread-based immunosensor (CT-IS), a biosensor to easily detect the presence of airborne viruses. CT-IS utilizes an antibody that specifically recognizes the HA protein of the pandemic influenza A (pH1N1) virus, which is incorporated into the conductive thread. The antigen-antibody interaction results in increased strain on the conductive thread in the presence of the pH1N1 virus, resulting in increased electrical resistance of the CT-IS. We evaluated the performance of this sensor using the HA protein and the pH1N1 virus, in addition to samples from patients infected with the pH1N1 virus. We observed a significant change in resistance in the pH1N1-infected patient samples (positive: n = 11, negative: n = 9), whereas negligible change was observed in the control samples (patients not infected with the pH1N1 virus; negative). Hence, the CT-IS is a lightweight fiber-type sensor that can be used as a wearable biosensor by combining it with textiles, to detect the pH1N1 virus in a person's vicinity.

Association of Physical Activity With Risk of Liver Fibrosis, Sarcopenia, and Cardiovascular Disease in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: International guidelines recommend physical activity for subjects with nonalcoholic fatty liver disease (NAFLD). This study investigated the association of physical activity with risk of liver fibrosis, sarcopenia, and cardiovascular disease (CVD) in NAFLD. METHODS: In this multicenter, retrospective study, 11,690 NAFLD subjects who underwent a health screening program and were assessed for physical activity (metabolic equivalent task [MET]-min/week) between 2014 and 2020 were recruited. Liver fibrosis was assessed by using the fibrosis-4 index, NAFLD fibrosis score, and FibroScan-AST score, sarcopenia by using multi-frequency bioelectric impedance analysis, and CVD risk by using atherosclerotic CVD (ASCVD) risk score, and coronary artery calcium (CAC) score were calculated. RESULTS: The prevalence of fibrosis, sarcopenia, high probability of ASCVD, and high CAC score significantly decreased with increasing quartiles of physical activity (all P for trend <.001). In a fully adjusted model, physical activity above 600 MET-min/week (≥third quartile) was independently associated with a reduced risk of fibrosis (adjusted odds ratio [aOR] = 0.59; 95% confidence interval [CI], 0.40-0.86), sarcopenia (aOR = 0.72; 95% CI, 0.58-0.88), high probability of ASCVD (aOR = 0.58; 95% CI, 0.46-0.73), and high CAC score (aOR = 0.32; 95% CI, 0.13-0.83; all P <.05). In addition, increasing amounts of physical activity were significantly associated with risk reduction between fibrosis, sarcopenia, and high probability of ASCVD (all P for trend <.001). In subjects with sarcopenic obesity or lean NAFLD, physical activity was also independently associated with reduced risk of fibrosis and high probability of ASCVD (all P <.05). CONCLUSIONS: Physical activity showed a protective effect against fibrosis, sarcopenia, and CVD in NAFLD.

Protected Health Information Recognition by Fine-Tuning a Pre-training Transformer Model.

OBJECTIVE: De-identifying protected health information (PHI) in medical documents is important, and a prerequisite to deidentification is the identification of PHI entity names in clinical documents. This study aimed to compare the performance of three pre-training models that have recently attracted significant attention and to determine which model is more suitable for PHI recognition. METHODS: We compared the PHI recognition performance of deep learning models using the i2b2 2014 dataset. We used the three pre-training models-namely, bidirectional encoder representations from transformers (BERT), robustly optimized BERT pre-training approach (RoBERTa), and XLNet (model built based on Transformer-XL)-to detect PHI. After the dataset was tokenized, it was processed using an inside-outside-beginning tagging scheme and WordPiecetokenized to place it into these models. Further, the PHI recognition performance was investigated using BERT, RoBERTa, and XLNet. RESULTS: Comparing the PHI recognition performance of the three models, it was confirmed that XLNet had a superior F1-score of 96.29%. In addition, when checking PHI entity performance evaluation, RoBERTa and XLNet showed a 30% improvement in performance compared to BERT. CONCLUSIONS: Among the pre-training models used in this study, XLNet exhibited superior performance because word embedding was well constructed using the two-stream self-attention method. In addition, compared to BERT, RoBERTa and XLNet showed superior performance, indicating that they were more effective in grasping the context.

Adaptive Conformal Cooling of Injection Molds Using Additively Manufactured TPMS Structures.

In injection molding, cooling channels are usually manufactured with a straight shape, and thus have low cooling efficiency for a curved mold. Recently, additive manufacturing (AM) was used to fabricate conformal cooling channels that could maintain a consistent distance from the curved surface of the mold. Because this conformal cooling channel was designed to obtain a uniform temperature on the mold surface, it could not efficiently cool locally heated regions (hot spots). This study developed an adaptive conformal cooling method that supports localized-yet-uniform cooling for the heated region by employing micro-cellular cooling structures instead of the typical cooling channels. An injection molding simulation was conducted to predict the locally heated region, and a mold core was designed to include a triply periodic minimal surface (TPMS) structure near the heated region. Two biomimetic TPMS structures, Schwarz-diamond and gyroid structures, were designed and fabricated using a digital light processing (DLP)-type polymer AM process. Various design parameters of the TPMS structures, the TPMS shapes and base coordinates, were investigated in terms of the conformal cooling performance. The mold core with the best TPMS design was fabricated using a powder-bed fusion (PBF)-type metal AM process, and injection molding experiments were conducted using the additively manufactured mold core. The developed mold with TPMS cooling achieved a 15 s cooling time to satisfy the dimensional tolerance, which corresponds to a 40% reduction in comparison with that of the conventional cooling (25 s).

Synbiotics Containing Nanoprebiotics: A Novel Therapeutic Strategy to Restore Gut Dysbiosis.

A new formulation, nanoprebiotics [e.g., phthalyl pullulan nanoparticles (PPNs)], was demonstrated to enhance the antimicrobial activity of probiotics [e.g., Lactobacillus plantarum (LP)] in vitro through intracellular stimulation better than that by backbone prebiotics, which are commonly used. In this study, we aimed to investigate whether this combination would exert distinct effects as synbiotics in vivo. Synbiotics combinations of LP, pullulan, and PPNs were used as experimental treatments in a dysbiosis-induced murine model, and their restorative effect was assessed using pathogen Escherichia coli K99 challenge. Our results showed that the E. coli infection was suppressed markedly in the experimental group fed with synbiotics containing PPNs. In addition, the decrease in serum endotoxin level after synbiotics treatment suggested the reinforcement of the gut barrier. Comparison of treatment groups, including a normal control group, showed that synbiotics containing PPNs increased microbial diversity, which is a representative parameter of healthy status. Furthermore, distinct from probiotics treatment alone, synbiotics showed additive effects of enrichment of several well-known beneficial bacteria such as Lactobacillus, Bifidobacterium, and other butyrate-producing bacteria including Faecalibacterium. Collectively, our results indicate that synbiotics containing PPNs are effective at restoring gut dysbiosis, suppressing pathogenic infection, and increasing microbial diversity, suggesting that synbiotics with nanoprebiotics have the potential to be a novel strategy for ameliorating gut dysbiosis and infectious diseases.

The anti-cancerous activity of adaptogenic herb Astragalus membranaceus.

BACKGROUND: Cancer is the most dreadful disease increasing rapidly causing an economic burden globally. A standardized chemotherapy regimen planned with curative intent weakens the immune system and damages healthy cells making the patient prone to infections and severe side effects with pain and fatigue. PURPOSE: Astragalus membranaceus (AM) has a long history of use in the treatment of severe adverse diseases. For thousands of years, it has been used in mixed herbal decoctions for the treatment of cancer. Due to growing interest in this plant root for its application to treat various types of cancers and tumors, has attracted researcher's interest. METHOD: The literature search was done from core collections of electronic databases such as Web of Science, Google Scholar, PubMed and Science Direct using keywords given below and terms like pharmacological and phytochemical details of this plant. OUTCOME: Astragalus membranaceus has demonstrated the ability to modulate the immune system during drug therapy making the patient physically fit and prolonged life. It has become a buzzword of herbalists as it is one of the best of seven important adaptogenic herbs with a protective effect against chronic stress and cancer. It demonstrated significant amelioration of the perilous toxic effects induced by concurrently administered chemo onco-drugs. CONCLUSION: The natural phytoconstituents of this plant formononetin, astragalus polysaccharide, and astragalosides which show high potential anti-cancerous activity are studied and discussed in detail. One of them are used in clinical trials to overcome cancer related fatigue. Overall, this review aims to provide an insight into Astragalus membranaceus status in cancer therapy.

Mechanical and Microscopic Characteristics of Polyurethane-Based Pervious Pavement Composites.

Conventional pervious pavement materials (PPM) that consist of cement and aggregate materials are known for poor durability due to their brittle behavior. Thus, to enhance the durability, we fabricated polymeric PPMs from durable and abundant polyurethane (PU) and undertook mechanical and microscopic characterizations. PU-based PPM samples with varying aggregate sizes were produced and examined to test their compressive strength and water permeability. Furthermore, X-ray micro-computed tomography (micro-CT) was implemented to analyze the samples' pore and tortuosity characteristics. Through the micro-CT analysis, the morphological characteristics of PPM's internal structures were identified and quantitively analyzed the correlations between the pore size distribution, connectivity, and tortuosity within the samples. Finally, the microstructures derived from micro-CT were generated as a finite element model and also numerically determined the stress distribution generated inside.

Cytoplasmic expression of a model antigen with M Cell-Targeting moiety in lactic acid bacteria and implication of the mechanism as a mucosal vaccine via oral route.

Lactic acid bacteria (LAB) have been widely studied as mucosal vaccine delivery carriers against many infectious diseases for heterologous expression of protein antigens. There are three antigen expression strategies for LAB: cytoplasmic expression (CE), cell surface display (SD), and extracellular secretion (ES). Despite the generally higher protein expression level and many observations of antigen-specific immunogenicity in CE, its application as a mucosal vaccine has been overlooked relative to SD and ES because of the antigens enclosed by the LAB cell wall. We hypothesized that the antigens in CE could be released from the LAB into the intestinal lumen before host bacterial access to gut-associated lymphoid tissue (GALT), which could contribute to antigen-specific immune responses after oral administration. To elucidate this hypothesis, three recombinant Lactobacillus plantarum (LP) strains were constructed to produce a model antigen, BmpB, with or without an M cell-targeting moiety, and their immunogenicities were analyzed comparatively as oral vaccines in mouse model. The data indicated that the recombinant LPs producing BmpBs with different conformations could induce mucosal immunity differentially. This suggests that the cytoplasmic antigens in LAB could be released into the intestinal lumen, subsequently translocated through M cells, and stimulate the GALT to generate antigen-specific immune responses. Therefore, the CE strategy has great potential, especially in the application of oral LAB vaccines as well as SD and ES strategies. This research provides a better understanding of the mechanism for recombinant oral LAB vaccines and gives insight to the future design of LAB vaccines and oral delivery applications for useful therapeutic proteins.

Fabrication of Carbon Disulfide Added Colloidal Gold Colorimetric Sensor for the Rapid and On-Site Detection of Biogenic Amines.

Meat is often wasted due to the perceived concerns of its shelf life and preservation. Specifically, in meat formation, biogenic amines (BAs) are the major agents to spoil them. Herein, we have developed a carbon disulfide (CS2) added colloidal gold nanoparticles-based colorimetric sensor for the rapid and on-site detection of biogenic amines. Transmission electron microscopy is used to observe the morphological changes in colloidal gold nanoparticles and aggregation behavior of CS2 added to the colloidal gold nanoparticles' solution. Raman spectroscopic analysis is further used to characterize the peaks of CS2, Cad and CS2-Cad molecules. Absorption spectroscopy is used to estimate the colorimetric differences and diffuse reflectance spectra of the samples. The sensing analysis is performed systematically in the presence and absence of CS2. CS2 added colloidal gold nanoparticles colorimetric sensor detected the BAs with a limit of detection (LOD) value of 50.00 µM. Furthermore, the developed sensor has shown an LOD of 50.00 µM for the detection of multiple BAs at a single time. The observed differences in the colorimetric and absorption signals indicate that the structure of BAs is converted to the dithiocarbamate (DTC)-BA molecule, due to the chemical reactions between the amine groups of BAs and CS2. Significantly, the developed colorimetric sensor offers distinct features such as facile fabrication approach, on-site sensing strategy, rapid analysis, visual detection, cost-effective, possibility of mass production, availability to detect multiple BAs at a single time and appreciable sensitivity. The developed sensor can be effectively used as a promising and alternative on-site tool for the estimation of BAs.

Sustained Exposure of Substance P Causes Tendinopathy.

Recently, neuromediators such as substance P (SP) have been found to be important factors in tendon homeostasis. Some studies have found SP to be the cause of inflammation and tendinopathy, whereas others have determined it to be a critical component of tendon healing. As demonstrated by these conflicting findings, the effects of SP on tendinopathy remain unclear. In this study, we hypothesized that the duration of SP exposure determines its effect on the tendons, with repetitive long-term exposure leading to the development of tendinopathy. First, we verified the changes in gene and protein expression using in vitro tenocytes with 10-day exposure to SP. SP and SP + Run groups were injected with SP in their Achilles tendon every other day for 14 days. Achilles tendons were then harvested for biomechanical testing and histological processing. Notably, tendinopathic changes with decreased tensile strength, as observed in the Positive Control, were observed in the Achilles in the SP group compared to the Negative Control. Subsequent histological analysis, including Alcian blue staining, also revealed alterations in the Achilles tendon, which were generally consistent with the findings of tendinopathy in SP and SP + Run groups. Immunohistochemical analysis revealed increased expression of SP in the SP group, similar to the Positive Control. In general, the SP + Run group showed worse tendinopathic changes. These results suggest that sustained exposure to SP may be involved in the development of tendinopathy. Future research on inhibiting SP is warranted to target SP in the treatment of tendinopathy and may be beneficial to patients with tendinopathy.

Long-Term Oral Bisphosphonate Compliance Focusing on Switching of Prescription Pattern.

BACKGROUND: Factors determining bisphosphonate compliance are not fully understood. We examined fluctuations in oral bisphosphonate dosing intervals to gauge therapeutic compliance in patients with osteoporosis. MATERIALS AND METHODS: Hospital data accruing between 2010 and 2017 were accessed to retrospectively study patients ≥50 years old (N=1873), each prescribed bisphosphonate at initial diagnosis of osteoporosis. The medication possession ratio (MPR), calculated as total days supplied divided by length of follow-up, served to measure therapeutic compliance. We compared MPRs of various prescription patterns (daily, weekly, monthly, and switch [ie, ≥1 change in pattern] groups). We also analyzed the impact of age, sex, fracture history, surgical history, and comorbidities. Multiple regression analysis was ultimately performed, using MPR as a dependent variable. RESULTS: In our cohort (mean follow-up=5.7±2.4 years), once weekly dosing was the most common prescription pattern (1223/1873, 65.3%), as opposed to monthly (366/1873, 19.5%) or daily (164/1873, 8.8%) dosing. A total of 120 patients (6.4%) comprising the switch group changed dosing patterns during the study period. MPR was significantly higher in the switch group (32.8±22.7) than in the other three groups (daily, 21.9±25.9; weekly, 22.7±27.3; monthly, 23.2±27.7). In multiple regression analysis, younger age (P<0.001), female sex (P=0.004), and switching of prescription pattern (decrease or increase frequency) were factors significantly associated with higher MPR, signaling better compliance. CONCLUSION: Better bisphosphonate compliance was associated with physician-modified dosing patterns. We therefore recommend adjustments of prescription intervals in poorly compliant patients requiring long-term treatment.

Improved conductivity of flower-like MnWO4 on defect engineered graphitic carbon nitride as an efficient electrocatalyst for ultrasensitive sensing of chloramphenicol.

Environmental hazards caused by chloramphenicol has attained special attention. Fast, accurate and reliable detection of chloramphenicol in foodstuffs and water samples is of utmost importance. Herein, we developed a g-C3N4/MnWO4 composite for the selective and sensitive detection of chloramphenicol. Successful fabrication of g-C3N4/MnWO4 composite was verified by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD) and x-ray photo electron spectroscopy (XPS) techniques. Electrochemical characteristics were evaluated by using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The g-C3N4/MnWO4 modified glassy carbon electrode has shown the highest electrocatalytic activity towards chloramphenicol with a decreased reduction potential of -0.547 V and increased cathodic peak current. The developed sensor has shown excellent performance for the detection of chloramphenicol with a sensitivity of 0.9986 µA nM-1 cm-2 and LOD of 1.03 nM in a broad linear range of 4.0-71 nM. In addition, the fabricated sensor has achieved anti-interference ability, good stability, excellent repeatability and remarkable reproducibility for the detection of chloramphenicol. The fabricated sensor applied for the determination of chloramphenicol in milk, human blood serum and sewage samples, in which significant and satisfactory results were achieved.