Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs ma...Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.展开更多
Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy r...Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.展开更多
Based on the features extracted from generalized autoregressive (GAR) model parameters of the received waveform, and the use of multilayer perceptron(MLP) neural network classifier, a new digital modulation recognitio...Based on the features extracted from generalized autoregressive (GAR) model parameters of the received waveform, and the use of multilayer perceptron(MLP) neural network classifier, a new digital modulation recognition method is proposed in this paper. Because of the better noise suppression ability of the GAR model and the powerful pattern classification capacity of the MLP neural network classifier, the new method can significantly improve the recognition performance in lower SNR with better robustness. To assess the performance of the new method, computer simulations are also performed.展开更多
Belize has the highest rates of HIV infection in Central America and is experiencing a generalized epidemic. The Garífuna, a minority ethnic population, is at risk for HIV. This study uses survey data from Gar...Belize has the highest rates of HIV infection in Central America and is experiencing a generalized epidemic. The Garífuna, a minority ethnic population, is at risk for HIV. This study uses survey data from Garífuna men and women to examine the frequency of multiple partnerships as well as sociodemographic characteristics and behavioral constructs correlated with having multiple partners. A high proportion of respondents reported having multiple partners, but rates were significantly higher for men, and men had a higher mean number of partners than women. A high proportion of respondents reported having a sexually transmitted infection (STI) in the last year, with more men reporting a history of STIs than women. Regression results show the importance of improving men and women’s perceived susceptibility for HIV and encouraging them to know their HIV status. Reinforcing a social norm for partner reduction would also benefit men. Study findings support the need for HIV counseling and testing in Garífuna communities as well as STI prevention, diagnosis and treatment. This study demonstrates that reducing multiple partnerships among Garífuna men and women is critical for reducing the spread of HIV in Belize.展开更多
The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid depe...The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.展开更多
Folk songs and dances originated from people's sacrificial activities in the struggle against nature in the primitive society.Their origins are related to the ideology and living environment of the people at that ...Folk songs and dances originated from people's sacrificial activities in the struggle against nature in the primitive society.Their origins are related to the ideology and living environment of the people at that period of time.These activities were expressed in the form of primitive songs and dances,and gradually evolved into folk songs and dances.The gar pa song and dance from Diebu,in Gannan region,is a unique song and dance of a Tibetan region on the eastern edge of Qinghai-Tibet Plateau.Its content and form are unique.It still retains the original trinity feature which includes poem,music,and dance.The production of songs and dances contains rich cultural connotations and unique local characteristics.This article elaborates the characteristics of Diebu's gar pa song and dance in terms of its music and performance form.展开更多
本试验旨在建立能同时检测猪流行性腹泻病毒(PEDV)、猪传染性胃肠炎病毒(TGEV)和猪A群轮状病毒(GAR)的多重RT-PCR检测方法。根据GenBank收录的PEDVM基因、TGEVN基因、GARVP7基因,利用软件Pri mer 5.0设计合成能分别特异性扩增PEDV、TGEV...本试验旨在建立能同时检测猪流行性腹泻病毒(PEDV)、猪传染性胃肠炎病毒(TGEV)和猪A群轮状病毒(GAR)的多重RT-PCR检测方法。根据GenBank收录的PEDVM基因、TGEVN基因、GARVP7基因,利用软件Pri mer 5.0设计合成能分别特异性扩增PEDV、TGEV、GAR相应基因的引物。利用这3对引物,作者建立了一种新的能够同时检测PEDV、TGEV和GAR的多重RT-PCR方法,并将这种方法和常规的RT-PCR进行了比较。实验室检测中,多重RT-PCR检测方法能够检测到35 pg的TGEV-PEDV-GAR三联苗的混合RNA。应用该方法检测了华中地区75份腹泻猪粪样,同时利用常规RT-PCR检测方法对该检测方法的敏感性和特异性进行了分析,结果表明该方法检测PEDV、TGEV、GAR的敏感性分别为92%、100%、100%,特异性均为100%。该方法敏感性高、特异性强,是一种新的检测PEDV、TGEV和GAR的方法。展开更多
Tropical mountain ranges shape the structure of tree communities and promote highly diverse natural habitats.The“Bosque Protector Chong on-Colonche”(BPCC),an 86,000-ha mountain formation situated on the coast of Ecu...Tropical mountain ranges shape the structure of tree communities and promote highly diverse natural habitats.The“Bosque Protector Chong on-Colonche”(BPCC),an 86,000-ha mountain formation situated on the coast of Ecuador,is biogeographically important for the region by connecting floristic elements of the wet Choco and the dry Tumbesian forests.Our understanding of the factors that model tree and palm diversity and distribution in this mountain range are limited.We measured and identified all trees and palms(DBH≥10 cm)in 289 plots of0.2 ha,distributed throughout BPCC.We used generalized linear models to explain the relationship between forest diversity and structure and climatic variables(temperature,rain,aridity),and altitude.We then used cluster and non-metric multidimensional scale(NMDS)analyses to search for distinct forest communities within the BPCC.Variance partition(varpart)was used to determine which predictor variables best explained these distinct forest communities.A species indicator analysis identified the species most likely to define these distinct forest communities.Finally,we carried out a niche modeling approach to identify the potential distribution of these forest communities within BPCC.In total,we identified 220 tree and palm species in our survey.The average number of species per plot was 17.8±5.8,ranging from 3 to 40 species.Classification methods sorted the 289study plots into six different forest communities,three communities in the dry forest and three in the semi-humid Garúa forest.Precipitation and temperature,but not altitude or aridity,explained floristic composition.These results emphasize the high but little cataloged diversity in the lowland mountain rainforests of coastal Ecuador.展开更多
基金supported by grants from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2019ZX09301159)the“Thousand Talent Program”for Science and Technology Innovation Leader in Henan(No.194200510002)+1 种基金the Bingtuan Science and Technology Project(No.2019AB034)the Natural Science Foundation of Henan Province of China(No.202300410381).
文摘Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.
文摘Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.
文摘Based on the features extracted from generalized autoregressive (GAR) model parameters of the received waveform, and the use of multilayer perceptron(MLP) neural network classifier, a new digital modulation recognition method is proposed in this paper. Because of the better noise suppression ability of the GAR model and the powerful pattern classification capacity of the MLP neural network classifier, the new method can significantly improve the recognition performance in lower SNR with better robustness. To assess the performance of the new method, computer simulations are also performed.
文摘Belize has the highest rates of HIV infection in Central America and is experiencing a generalized epidemic. The Garífuna, a minority ethnic population, is at risk for HIV. This study uses survey data from Garífuna men and women to examine the frequency of multiple partnerships as well as sociodemographic characteristics and behavioral constructs correlated with having multiple partners. A high proportion of respondents reported having multiple partners, but rates were significantly higher for men, and men had a higher mean number of partners than women. A high proportion of respondents reported having a sexually transmitted infection (STI) in the last year, with more men reporting a history of STIs than women. Regression results show the importance of improving men and women’s perceived susceptibility for HIV and encouraging them to know their HIV status. Reinforcing a social norm for partner reduction would also benefit men. Study findings support the need for HIV counseling and testing in Garífuna communities as well as STI prevention, diagnosis and treatment. This study demonstrates that reducing multiple partnerships among Garífuna men and women is critical for reducing the spread of HIV in Belize.
文摘The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.
文摘Folk songs and dances originated from people's sacrificial activities in the struggle against nature in the primitive society.Their origins are related to the ideology and living environment of the people at that period of time.These activities were expressed in the form of primitive songs and dances,and gradually evolved into folk songs and dances.The gar pa song and dance from Diebu,in Gannan region,is a unique song and dance of a Tibetan region on the eastern edge of Qinghai-Tibet Plateau.Its content and form are unique.It still retains the original trinity feature which includes poem,music,and dance.The production of songs and dances contains rich cultural connotations and unique local characteristics.This article elaborates the characteristics of Diebu's gar pa song and dance in terms of its music and performance form.
文摘本试验旨在建立能同时检测猪流行性腹泻病毒(PEDV)、猪传染性胃肠炎病毒(TGEV)和猪A群轮状病毒(GAR)的多重RT-PCR检测方法。根据GenBank收录的PEDVM基因、TGEVN基因、GARVP7基因,利用软件Pri mer 5.0设计合成能分别特异性扩增PEDV、TGEV、GAR相应基因的引物。利用这3对引物,作者建立了一种新的能够同时检测PEDV、TGEV和GAR的多重RT-PCR方法,并将这种方法和常规的RT-PCR进行了比较。实验室检测中,多重RT-PCR检测方法能够检测到35 pg的TGEV-PEDV-GAR三联苗的混合RNA。应用该方法检测了华中地区75份腹泻猪粪样,同时利用常规RT-PCR检测方法对该检测方法的敏感性和特异性进行了分析,结果表明该方法检测PEDV、TGEV、GAR的敏感性分别为92%、100%、100%,特异性均为100%。该方法敏感性高、特异性强,是一种新的检测PEDV、TGEV和GAR的方法。
文摘Tropical mountain ranges shape the structure of tree communities and promote highly diverse natural habitats.The“Bosque Protector Chong on-Colonche”(BPCC),an 86,000-ha mountain formation situated on the coast of Ecuador,is biogeographically important for the region by connecting floristic elements of the wet Choco and the dry Tumbesian forests.Our understanding of the factors that model tree and palm diversity and distribution in this mountain range are limited.We measured and identified all trees and palms(DBH≥10 cm)in 289 plots of0.2 ha,distributed throughout BPCC.We used generalized linear models to explain the relationship between forest diversity and structure and climatic variables(temperature,rain,aridity),and altitude.We then used cluster and non-metric multidimensional scale(NMDS)analyses to search for distinct forest communities within the BPCC.Variance partition(varpart)was used to determine which predictor variables best explained these distinct forest communities.A species indicator analysis identified the species most likely to define these distinct forest communities.Finally,we carried out a niche modeling approach to identify the potential distribution of these forest communities within BPCC.In total,we identified 220 tree and palm species in our survey.The average number of species per plot was 17.8±5.8,ranging from 3 to 40 species.Classification methods sorted the 289study plots into six different forest communities,three communities in the dry forest and three in the semi-humid Garúa forest.Precipitation and temperature,but not altitude or aridity,explained floristic composition.These results emphasize the high but little cataloged diversity in the lowland mountain rainforests of coastal Ecuador.
