The importance of individual beliefs in assessing treatment efficacy.

In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual's subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non-clinical research to start accounting for participants' subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions.

Neuromodulation is a type of intervention that relies on various non-invasive techniques to temporarily stimulate the brain and nervous system. It can be used for the treatment of depression or other medical conditions, as well as the improvement of cognitive abilities such as attention. However, there is conflicting evidence regarding whether this approach has beneficial effects. Most studies aiming to assess the efficiency of a treatment rely on examining the outcomes of people who received the intervention in comparison to participants who undergo a similar procedure with no therapeutic effect (or placebo). However, the influence of other, 'subjective' factors on these results ­ such as the type of intervention participants think they have received ­ remains poorly investigated. To bridge this gap, Fassi and Hochman et al. used statistical modeling to assess how patients' beliefs about their treatment affected the results of four neuromodulation studies on mind wandering, depression and attention deficit hyperactivity disorder symptoms. In two studies, participants' perceptions of their treatment status were more strongly linked to changes in depression scores and mind-wandering than the actual treatment. Results were more nuanced in the other two studies. In one of them, participants who received the real neuromodulation but believed they received the placebo showed the most improvement in depressive symptoms; in the other study, subjective beliefs and objective treatment both explained changes in inattention symptoms. Taken together, the results by Fassi and Hochman et al. suggest that factoring in patients' subjective beliefs about their treatment may be necessary in studies of neuromodulation and other interventions like virtual reality or neurofeedback, where participants are immersed in cutting-edge research settings and might therefore be more susceptible to develop beliefs about treatment efficacy.

Taste shaped the use of botanical drugs.

The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also referred to as chemosensation, enables animals to find high-value foods and avoid toxins. Humans have learned to use unpalatable and toxic substances as medicines, yet the importance of chemosensation in this process is poorly understood. Here, we generate tasting-panel data for botanical drugs and apply phylogenetic generalised linear mixed models to test whether intensity and complexity of chemosensory qualities as well as particular tastes and flavours can predict ancient Graeco-Roman drug use. We found chemosensation to be strongly predictive of therapeutic use: botanical drugs with high therapeutic versatility have simple yet intense tastes and flavours, and 21 of 22 chemosensory qualities predicted at least one therapeutic use. In addition to the common notion of bitter tasting medicines, we also found starchy, musky, sweet, and soapy drugs associated with versatility. In ancient Greece and Rome, illness was thought to arise from imbalance in bodily fluids or humours, yet our study suggests that uses of drugs were based on observed physiological effects that are often consistent with modern understanding of chemesthesis and taste receptor pharmacology.

In ancient times people used trial and error to identify medicinal plants as being effective. Later, diseases were believed to arise from imbalances in body fluids (or 'humours'), and botanical drugs were thought to restore this balance through the power of their taste. Modern science rejects this theory but does recognise the importance of chemosensation ­ our sensitivity to chemicals through taste and smell. These senses evolved in humans to help us seek out nutrients and avoid toxins and may also have guided the ancient uses of botanical drugs. There are many records of historical medicinal plant use and ailments, which makes it possible to explore possible relationships between therapeutic uses of botanical drugs and their chemosensory qualities. To investigate if therapeutic uses of botanical drugs could indeed be predicted by taste and flavour, Leonti, Baker et al. collected 700 botanical drugs identified in an ancient text, named De Materia Medica, which dates back to the 1^st century CE. The researchers asked volunteer tasters to classify the botanical drugs using 22 taste descriptions, such as bitter, aromatic, burning/hot, and fresh/cooling. The volunteers were also asked to score the strength of these tastes. Leonti, Baker et al. then used statistical modelling to see if the participant's taste descriptions could be used to predict the therapeutic uses of the drugs identified in the ancient text. This revealed that of the 46 therapeutic indications described in the text, 45 showed significant associations with at least one taste quality. Botanical drugs with stronger and simpler tastes tended to be used for a wider range of therapeutic indications. This suggests that chemosensation influenced therapeutic expectations in ancient, prescientific medicine. The study of Leonti, Baker et al. brings ancient medicine to life, offering valuable insights into the chemosensory aspects of medicinal plants and their potential applications in modern medicine. A next step would be to explore whether these insights could have relevance to modern science.

Navigating the path of TOF- A Literature review unveiling maternal-fetal dynamics, treatment strategies and psychological dimensions.

Tetralogy of Fallot (TOF) is a complex congenital heart defect that poses unique challenges for both mothers and their unborn children. This comprehensive review, aims to provide a holistic exploration of the maternal-fetal dynamics, treatment strategies, and psychological dimensions involved in navigating the path of TOF during pregnancy. It delves into the physiological changes that occur during pregnancy in TOF patients, including pulmonary regurgitation, right ventricular hypertrophy, and the overriding aorta. By understanding these dynamics, healthcare professionals can tailor treatment strategies to optimize maternal and fetal outcomes. The review further investigates the treatment strategies employed in managing TOF during pregnancy, encompassing medical interventions, cardiac monitoring, and multidisciplinary care. It explores the role of advanced imaging techniques, such as echocardiography and cardiac magnetic resonance imaging, in assessing TOF severity and guiding treatment decisions. The psychological factors influencing maternal adaptation, coping strategies, and the long-term implications on the child's psychological development are also examined. The integration of multidisciplinary approaches, including cardiac care, psychosocial support, and mental health interventions, can orchestrate a harmonious symphony of maternal-fetal well-being in the challenging journey of TOF pregnancies. Future research endeavours should continue to explore these dimensions, further refining treatment strategies and enhancing the understanding of TOF pregnancies for improved outcomes.

New method of producing a more efficient coagulant for the treatment of water from seeds of moringa oleifera.

The coagulation is essential in raw water treatment. The most used coagulants are often of chemical origin and expensive and their use generates non-biodegradable residues. This is why innovative studies on the synthesis of natural coagulants based on plant extracts are very important. This study presents a new method of producing a coagulant for the treatment of water from seeds of moringa oleifera. The application of the new method is done in several steps: Harvesting moringa oleifera seeds, shelling, crushing the seeds, extracting oil from moringa oleifera powder, extracting salts from powder from moringa seeds oleifera, microfiltration with a 0.2 µm filter and lyophilization which gives the final product in dry form. We used the resulting product for coagulation of lake water with an initial turbidity of 40 NTU. This treatment reduced the turbidity of the water by almost 95 % when we used 0.7 mg of this coagulant per liter of water. Moringa has previously been used to produce coagulant but the peculiarity of this study is that it takes a very small amount of the synthesized product to effectively treat water. -The results of this research work have shown that the coagulant produced rom the seeds of Moringa oleifera can be used effectively for the treatment of surface water.-The residual turbidity obtained after the treatment of lake water with the coagulant produced was in accordance with the drinking water standard according to the World Health Organization (WHO) (less than 5 NTU).-The coagulant produced by this new method from moringa oleifera seed is an alternative to aluminum sulfate coagulant for water treatment.

Development and biophysical characterization of a humanized FSH-blocking monoclonal antibody therapeutic formulated at an ultra-high concentration.

Highly concentrated antibody formulations are oftentimes required for subcutaneous, self-administered biologics. Here, we report the development of a unique formulation for our first-in-class FSH-blocking humanized antibody, MS-Hu6, which we propose to move to the clinic for osteoporosis, obesity, and Alzheimer's disease. The studies were carried out using our Good Laboratory Practice (GLP) platform, compliant with the Code of Federal Regulations (Title 21, Part 58). We first used protein thermal shift, size exclusion chromatography, and dynamic light scattering to examine MS-Hu6 concentrations between 1 and 100 mg/mL. We found that thermal, monomeric, and colloidal stability of formulated MS-Hu6 was maintained at a concentration of 100 mg/mL. The addition of the antioxidant L-methionine and chelating agent disodium EDTA improved the formulation's long-term colloidal and thermal stability. Thermal stability was further confirmed by Nano differential scanning calorimetry (DSC). Physiochemical properties of formulated MS-Hu6, including viscosity, turbidity, and clarity, confirmed with acceptable industry standards. That the structural integrity of MS-Hu6 in formulation was maintained was proven through Circular Dichroism (CD) and Fourier Transform Infrared (FTIR) Spectroscopy. Three rapid freeze-thaw cycles at -80 °C/25 °C or -80 °C/37 °C further revealed excellent thermal and colloidal stability. Furthermore, formulated MS-Hu6, particularly its Fab domain, displayed thermal and monomeric storage stability for more than 90 days at 4°C and 25°C. Finally, the unfolding temperature (Tm) for formulated MS-Hu6 increased by >4.80 °C upon binding to recombinant FSH, indicating highly specific ligand binding. Overall, we document the feasibility of developing a stable, manufacturable and transportable MS-Hu6 formulation at a ultra-high concentration at industry standards. The study should become a resource for developing biologic formulations in academic medical centers.

The effect of calcium supplementation in people under 35 years old: A systematic review and meta-analysis of randomized controlled trials.

Background: The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years). Methods: This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old. Results: This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008-0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20-35 years) than the pre-PBM population (<20 years). Conclusions: Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis. Funding: This work was supported by Wenzhou Medical University grant [89219029].

Osteoporosis and bone fractures are common problems among older people, particularly older women. These conditions cause disability and reduce quality of life. Progressive loss of bone mineral density is usually the culprit. So far, strategies to prevent bone weakening with age have produced disappointing results. For example, taking calcium supplements in later life only slightly reduces the risk of osteoporosis or fracture. New approaches are needed. Bone mass increases gradually early in life and peaks and plateaus around 20-35 years of age. After that period, bone mass slowly declines. Some scientists suspect that increasing calcium intake during this period of peak bone mass may reduce osteoporosis or fracture risk later in life. A meta-analysis by Liu, Le et al. shows that boosting calcium intake in young adulthood strengthens bones. The researchers analyzed data from 43 randomized controlled trials that enrolled 7,382 participants. About half the studies looked at the effects of taking calcium supplements and the other half analyzed the effects of a high calcium diet. Boosting calcium intake in people younger than age 35 improved bone mineral density throughout the body. It also increased bone mineral density at the femoral neck, where most hip fractures occur. Calcium supplementation produced larger effects in individuals between the ages of 20 and 35 than in people younger than 20. Both high calcium diets and calcium supplements with doses less than 1000 mg/d boosted bone strength. Higher dose calcium supplements did not provide any extra benefits. The analysis suggests people should pay more attention to bone health during early adulthood. Large randomized clinical trials are needed to confirm the long-term benefits of boosting calcium intake during early adulthood. But if the results are validated, taking calcium supplements, or eating more calcium-rich foods between the ages of 20 and 35 may help individuals build healthier bones and prevent fractures and osteoporosis later in life.

Wild cereal grain consumption among Early Holocene foragers of the Balkans predates the arrival of agriculture.

Forager focus on wild cereal plants has been documented in the core zone of domestication in southwestern Asia, while evidence for forager use of wild grass grains remains sporadic elsewhere. In this paper, we present starch grain and phytolith analyses of dental calculus from 60 Mesolithic and Early Neolithic individuals from five sites in the Danube Gorges of the central Balkans. This zone was inhabited by likely complex Holocene foragers for several millennia before the appearance of the first farmers ~6200 cal BC. We also analyzed forager ground stone tools (GSTs) for evidence of plant processing. Our results based on the study of dental calculus show that certain species of Poaceae (species of the genus Aegilops) were used since the Early Mesolithic, while GSTs exhibit traces of a developed grass grain processing technology. The adoption of domesticated plants in this region after ~6500 cal BC might have been eased by the existing familiarity with wild cereals.

Before humans invented agriculture and the first farmers appeared in southwestern Asia, other ancient foragers (also known as hunter-gatherers) in southeastern Europe had already developed a taste for consuming wild plants. There is evidence to suggest that these foragers were intensely gathering wild cereal grains before the arrival of agriculture. However, until now, the only place outside southwestern Asia this has been shown to have occurred is in Greece, and is dated around 20,000 years ago. In the past, researchers proposed that forager societies in the Balkans also consumed wild cereals before transitioning to agriculture. But this has been difficult to prove because plant foods are less likely to preserve than animal bones and teeth, making them harder to detect in prehistoric contexts. To overcome this, Cristiani et al. studied teeth from 60 individuals found in archaeological sites between Serbia and Romania, which are attributed to the Mesolithic and Early Neolithic periods. Food particles extracted from crusty deposits on the teeth (called the dental calculus) were found to contain structures typically found in plants. In addition, Cristiani et al. discovered similar plant food residues on ground stone tools which also contained traces of wear associated with the processing of wild cereals. These findings suggest that foragers in the central Balkans were already consuming certain species of wild cereal grains 11,500 years ago, before agriculture arrived in Europe. It is possible that sharing knowledge about plant resources may have helped introduce domesticated plant species in to this region as early as 6500 BC. This work challenges the deep-rooted idea that the diet of hunter-gatherers during the Palaeolithic and Mesolithic periods primarily consisted of animal proteins. In addition, it highlights the active role the eating habits of foragers might have played in introducing certain domesticated plant species that have become primary staples of our diet today.

Multi-syndrome, multi-gene risk modeling for individuals with a family history of cancer with the novel R package PanelPRO.

Identifying individuals who are at high risk of cancer due to inherited germline mutations is critical for effective implementation of personalized prevention strategies. Most existing models focus on a few specific syndromes; however, recent evidence from multi-gene panel testing shows that many syndromes are overlapping, motivating the development of models that incorporate family history on several cancers and predict mutations for a comprehensive panel of genes.We present PanelPRO, a new, open-source R package providing a fast, flexible back-end for multi-gene, multi-cancer risk modeling with pedigree data. It includes a customizable database with default parameter values estimated from published studies and allows users to select any combinations of genes and cancers for their models, including well-established single syndrome BayesMendel models (BRCAPRO and MMRPRO). This leads to more accurate risk predictions and ultimately has a high impact on prevention strategies for cancer and clinical decision making. The package is available for download for research purposes at https://projects.iq.harvard.edu/bayesmendel/panelpro.

Genetic mutations that increase cancer risk can be passed down from parents to their children, which can affect families across many generations. In these families, multiple members may be affected by different types of cancer, and these cancers often develop at an early age. Unaffected family members are often referred to genetic counselling, where they can explore their own risk of cancer. Clinicians and genetic counselors can provide recommendations to minimize cancer risk and inform personal choices on how to manage that risk, such as opting for preventative surgeries or participating in regular screening. In genetic counselling sessions, highly trained clinicians and specialists use software that takes an individual's family history of cancer and uses it to estimate their individual risk of carrying certain genetic mutations. These estimates can in turn help to predict their future risk of cancer. Many existing software packages are limited to estimating risks based on mutations in well-known cancer-related genes, such as BRCA1 and BRCA2 in breast and ovarian cancer. However, emerging evidence suggests that many of the genes associated with cancer risk work as part of a complex and overlapping network. Since current risk-profiling software packages are only designed to consider such genes in isolation, they cannot generate the most robust, accurate or comprehensive cancer risk profiles. To address this challenge, Lee, Liang et al. have developed a new risk-profiling software that can integrate a large number of gene mutations and a wide range of potential cancer types to provide more accurate estimates of individual cancer risk. This software, called PanelPRO, uses evidence identified from extensive literature reviews to model the complex interplay between genes and cancer risk. The software not only calculates risks based on known genes, but also allows other developers to integrate new cancer-related genes that may be identified in the future. Importantly, the software is compatible with genetic counselling applications, since it returns answers within seconds when reasonable family and gene database sizes are used. PanelPRO is a new, modern, flexible and efficient software package that provides an important advance towards modelling the vast genetic and biological complexity that contributes to inherited cancer risk. This software is designed to provide a more accurate and comprehensive estimate of cancer risk for individuals with family histories of cancer. As an open-source software, it is freely available for research purposes, and can be licensed by software companies and healthcare organizations to integrate electronic patient records and rapidly identify at-risk individuals across larger patient groups. Ultimately, this software has the potential to improve cancer prevention strategies and optimize the personalized decision-making processes around cancer risk.

Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones.

Hsp70 molecular chaperones are abundant ATP-dependent nanomachines that actively reshape non-native, misfolded proteins and assist a wide variety of essential cellular processes. Here, we combine complementary theoretical approaches to elucidate the structural and thermodynamic details of the chaperone-induced expansion of a substrate protein, with a particular emphasis on the critical role played by ATP hydrolysis. We first determine the conformational free-energy cost of the substrate expansion due to the binding of multiple chaperones using coarse-grained molecular simulations. We then exploit this result to implement a non-equilibrium rate model which estimates the degree of expansion as a function of the free energy provided by ATP hydrolysis. Our results are in quantitative agreement with recent single-molecule FRET experiments and highlight the stark non-equilibrium nature of the process, showing that Hsp70s are optimized to effectively convert chemical energy into mechanical work close to physiological conditions.

Non-enzymatic primer extension with strand displacement.

Non-enzymatic RNA self-replication is integral to the emergence of the 'RNA World'. Despite considerable progress in non-enzymatic template copying, demonstrating a full replication cycle remains challenging due to the difficulty of separating the strands of the product duplex. Here, we report a prebiotically plausible approach to strand displacement synthesis in which short 'invader' oligonucleotides unwind an RNA duplex through a toehold/branch migration mechanism, allowing non-enzymatic primer extension on a template that was previously occupied by its complementary strand. Kinetic studies of single-step reactions suggest that following invader binding, branch migration results in a 2:3 partition of the template between open and closed states. Finally, we demonstrate continued primer extension with strand displacement by employing activated 3'-aminonucleotides, a more reactive proxy for ribonucleotides. Our study suggests that complete cycles of non-enzymatic replication of the primordial genetic material may have been facilitated by short RNA oligonucleotides.

Hypothesis, analysis and synthesis, it's all Greek to me.

The linguistic foundations of science and technology include many terms that have been borrowed from ancient languages. In the case of terms with origins in the Greek language, the modern meaning can often differ significantly from the original one. Here we use the PubMed database to demonstrate the prevalence of words of Greek origin in the language of modern science, and call for scientists to exercise care when coining new terms.

Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents.

Secondary metabolites from lichens are known for exhibiting various biological effects such as anti-inflammatory, antioxidant and antibacterial activities. Despite this wide range of reported biological effects, their impact on the formation of advanced glycation end products (AGEs) remains vastly unexplored. The latter are known contributors to lifestyle and age-related diseases such as Alzheimer and Parkinson. Moreover, the development of atherosclerosis and arterial stiffness is causally linked to the formation of AGEs. With this in mind, the present work evaluated the inhibitory effects of secondary lichen metabolites on the formation of pentosidine-like AGEs' by using an in vitro, Maillard reaction based, fluorescence assay. Overall, thirty-seven natural and five synthetically modified compounds were tested, eighteen of which exhibiting IC50 values in the range of 0.05 to 0.70 mM. This corresponds to 2 to 32 fold of the inhibitory activity of aminoguanidine. Targeting one major inhibiting mechanism of AGEs formation, all compounds were additionally evaluated on their radical scavenging capacities in an DPPH assay. Furthermore, as both AGEs' formation and hypertension are major risk factors for atherosclerosis, compounds that were available in sufficient amounts were also tested for their vasodilative effects. Overall, and though some of the active compounds were previously reported cytotoxic, present results highlight the interesting potential of secondary lichen metabolites as anti-AGEs and vasodilative agents.

A neural-level model of spatial memory and imagery.

We present a model of how neural representations of egocentric spatial experiences in parietal cortex interface with viewpoint-independent representations in medial temporal areas, via retrosplenial cortex, to enable many key aspects of spatial cognition. This account shows how previously reported neural responses (place, head-direction and grid cells, allocentric boundary- and object-vector cells, gain-field neurons) can map onto higher cognitive function in a modular way, and predicts new cell types (egocentric and head-direction-modulated boundary- and object-vector cells). The model predicts how these neural populations should interact across multiple brain regions to support spatial memory, scene construction, novelty-detection, 'trace cells', and mental navigation. Simulated behavior and firing rate maps are compared to experimental data, for example showing how object-vector cells allow items to be remembered within a contextual representation based on environmental boundaries, and how grid cells could update the viewpoint in imagery during planning and short-cutting by driving sequential place cell activity.

Experimental and observational studies find contrasting responses of soil nutrients to climate change.

Manipulative experiments and observations along environmental gradients, the two most common approaches to evaluate the impacts of climate change on nutrient cycling, are generally assumed to produce similar results, but this assumption has rarely been tested. We did so by conducting a meta-analysis and found that soil nutrients responded differentially to drivers of climate change depending on the approach considered. Soil carbon, nitrogen, and phosphorus concentrations generally decreased with water addition in manipulative experiments but increased with annual precipitation along environmental gradients. Different patterns were also observed between warming experiments and temperature gradients. Our findings provide evidence of inconsistent results and suggest that manipulative experiments may be better predictors of the causal impacts of short-term (months to years) climate change on soil nutrients but environmental gradients may provide better information for long-term correlations (centuries to millennia) between these nutrients and climatic features. Ecosystem models should consequently incorporate both experimental and observational data to properly assess the impacts of climate change on nutrient cycling.

Effect analysis of Naokang Ⅱ combined with aniracetam for patients with vascular cognitive impairment of none dementia after cerebral infarction / 中国脑血管病杂志

Objective To observe the clinical efficacy of Naokang Ⅱ in patients with vascular cognitive impairment of none dementia after cerebral infarction.Methods A total of 100 consecutive patients with vascular cognitive impairment of none dementia after cerebral infarction diagnosed at the Neurology Clinic,Beijing Xuanwu Hospital,Capital Medical University from October 2012 to February 2014 were enrolled prospectively.Six of them did not complete a return visit because of not returning to the hospital in time,2 withdrew automatically,and finally,92 patients were enrolled in the study.According to the random number table method,they were divided into either an observation group (n=48) or a control group (n=44).The control group was treated with aniracetam,while the observation group was treated with aniracetam plus Naokang Ⅱ (Radix Polygoni Multiflori Preparata,Radix Rehmanniae Preparata,Radix Notoginseng,Acorus Calamus L.and Radix Polygalae) for 12 weeks.The differences of traditional Chinese medicine syndrome integral before and after treatment in both groups were compared.The effective rate and cognitive function improvement rate of traditional Chinese medicine syndromes before and after treatment in both groups were compared.Results The scores of traditional Chinese medicine syndrome integral before and after treatment in patients of the observation group were 28±5 and 15±4,respectively,those of the control group before and after treatment were 26±5 and 18±5,respectively.There were significant differences before and after treatment (the t values were 15.02 and 14.73,respectively,all P0.05).The total effective rate in the observation group (75.0% [36/48]) was higher than that in the control group (45.5% [20/44]).There was significant difference between two groups (χ2=7.023,P=0.008).The improvement rates of memory,orientation,judgment,and problem solving skills in the observation group (29.2% [14/48],27.1% [13/48],and 31.2% [15/48]) were higher than those in the control group (11.4% [5/44],9.1% [4/44],and 13.6% [6/44]).There were significant differences between the two groups (all P<0.05).No adverse reactions were observed in the two groups during the observation period.Conclusion Naokang Ⅱ combined with aniracetam for patients with vascular cognitive impairment of none dementia after cerebral infarction had a synergistic effect.

Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation.

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases.

Effectiveness of Aloe Vera and Antioxidant along with Physiotherapy in the Management of Oral Submucous Fibrosis.

BACKGROUND: Oral submucous fibrosis (OSMF) is a well-established precancerous condition affecting the oral mucosa. It is a disease that causes significant morbidity (in terms of loss of mouth function as tissues become rigid and mouth opening becomes difficult) and mortality (when transformation into squamous cell carcinoma occurs). AIM: The aim of the study is to compare the efficacy of Aloe vera with antioxidant when given along with physiotherapy in the management of OSMF. MATERIALS AND METHODS: Forty patients presenting with clinical signs and symptoms of OSMF were included for the study after informed consent. Group A included 20 patients who received Aloe vera gel (forever living gel) along with physiotherapy. Group B included 20 patients who received antioxidant capsules twice daily for 3 months along with physiotherapy exercises four times in a day. The following parameters, that is, burning sensation, mouth opening, tongue protrusion and cheek flexibility were recorded at each visit. RESULTS: Majority of the participant enrolled were in the age range of 30 to 35 years. Improvement in all the parameters was seen with the individuals receiving Aloe vera gel in comparison to antioxidants. CONCLUSION: So, Aloe vera being a soothing, simple and safe mode of treatment along with proper habit restriction can be considered to be an effectual protocol in the management of OSMF. The analgesic effects of Aloe vera with the physiotherapy exercises provide better results in reducing burning sensation and improving mouth opening, tongue protrusion and cheek flexibility in comparison to antioxidants.

Post-infectious and non post-infectious irritable bowel syndrome: A comparative study.

OBJECTIVE: To compare the post-infectious irritable bowel syndrome (PI-IBS) and none post-infectious irritable bowel syndrome (NPI-IBS) clinically and experimentally. METHODS: From May 2013 to January 2015, eighty-nine patients with irritable bowel syndrome (IBS)were recruited in the internal department of the affiliated hospital of Shandong University of Traditional Chinese Medicine. The clinical data were collected for all the patients, and a blood sample was collected to detect the level of C-reactive protein (CRP) and intestinal fatty acid binding protein (IFABP), an investigation questionnaire of gastrointestinal symptom rating scale (GSRS) and self-rating anxiety scale (SAS) were carried out to evaluate the gastrointestinal function and anxiety status. RESULTS: In the study, forty-eight patients were included in PI-IBS group and 41 in Non-PI-IBS group. There was no significant difference in age, gender and GSRS between the two groups (p>0.05). In PI-IBS group 70.8% patients presented with the primary symptom of diarrhea and 60.4% presented with a SAS scores over 50, but in Non-PI-IBS group, the values were only 19% (p<0.05) and 34.1% (p<0.05). The level of IFABP and CRP were significantly higher in PI-IBS group than those in Non-PI-IBS group (p<0.05). CONCLUSION: The PI-IBS may be different from Non-PI-IBS in mechanism and should be treated using different strategies.

Efficacy of lignocaine in gel and spray form during buccal infiltration anesthesia in children: a randomized clinical trial.

AIM: To compare the efficacy of 15% lignocaine spray and 8% lignocaine gel as a topical anesthetic, in reducing pain, during buccal infiltration in children. MATERIALS AND METHODS: Forty-two patients aged between 7 and 12 years requiring restorative procedures/extraction/pulp therapy of primary/ permanent teeth in the maxillary arch, under buccal infiltration anesthesia were selected for the study. The participants were randomly allocated into 2 groups of 21 each. In group A, 8% lignocaine gel and in group B, 15% lignocaine spray was applied prior to buccal infiltration. Pain was assessed using Wong-Baker faces pain rating scale (WBFPRS) and faces legs activity cry and consolability (FLACC) painscale. RESULTS: Pearson's chi-square test revealed that there was no significant difference in the FLACC scores of the two groups (p = 0.54). Independent t-test demonstrated that there was no significant difference in Wong-Bakers faces pain score between the two agents (p = 0.07). CONCLUSION: There is no significant difference in the efficacy of 15% lignocaine spray and 8% lignocaine gel as a topical anesthetic in controlling pain during buccal infiltration anesthesia, in children.

Evaluation of medicinal interventions for the management of oral submucous fibrosis: a systematic review of the literature.

Oral submucous fibrosis is a chronic, progressive scarring disease associated with both significant morbidity including pain and limited mouth opening and an increased risk for malignancy. This systematic review evaluated the different medicinal (i.e. nonsurgical) interventions available for the management of oral submucous fibrosis. An automated literature searches of online databases from January 1960 to December 2013 were performed and only studies with high level of evidence based on the guidelines of the Oxford Centre for evidence-based medicine were selected. Thirteen studies (3 randomized controlled trials and 10 clinical trials/controlled clinical trials) were included and drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene were used. There is a clear lack of evidence on the available drug treatment for oral submucous fibrosis and further high quality randomized controlled trials are needed to evaluate the different therapeutic agents.