Early recognition of multiple sclerosis using natural language processing of the electronic health record.

BACKGROUND: Diagnostic accuracy might be improved by algorithms that searched patients' clinical notes in the electronic health record (EHR) for signs and symptoms of diseases such as multiple sclerosis (MS). The focus this study was to determine if patients with MS could be identified from their clinical notes prior to the initial recognition by their healthcare providers. METHODS: An MS-enriched cohort of patients with well-established MS (n = 165) and controls (n = 545), was generated from the adult outpatient clinic. A random sample cohort was generated from randomly selected patients (n = 2289) from the same adult outpatient clinic, some of whom had MS (n = 16). Patients' notes were extracted from the data warehouse and signs and symptoms mapped to UMLS terms using MedLEE. Approximately 1000 MS-related terms occurred significantly more frequently in MS patients' notes than controls'. Synonymous terms were manually clustered into 50 buckets and used as classification features. Patients were classified as MS or not using Naïve Bayes classification. RESULTS: Classification of patients known to have MS using notes of the MS-enriched cohort entered after the initial ICD9[MS] code yielded an ROC AUC, sensitivity, and specificity of 0.90 [0.87-0.93], 0.75[0.66-0.82], and 0.91 [0.87-0.93], respectively. Similar classification accuracy was achieved using the notes from the random sample cohort. Classification of patients not yet known to have MS using notes of the MS-enriched cohort entered before the initial ICD9[MS] documentation identified 40% [23-59%] as having MS. Manual review of the EHR of 45 patients of the random sample cohort classified as having MS but lacking an ICD9[MS] code identified four who might have unrecognized MS. CONCLUSIONS: Diagnostic accuracy might be improved by mining patients' clinical notes for signs and symptoms of specific diseases using NLP. Using this approach, we identified patients with MS early in the course of their disease which could potentially shorten the time to diagnosis. This approach could also be applied to other diseases often missed by primary care providers such as cancer. Whether implementing computerized diagnostic support ultimately shortens the time from earliest symptoms to formal recognition of the disease remains to be seen.

Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains.

Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141-145. Heavy- and light-chain phylogenetic trees of PGT141-145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141-145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings.

Increased stability and size of a bubble on a superhydrophobic surface.

Computational and theoretical models of millimeter-sized bubbles placed on upright hydrophobic and superhydrophobic surfaces are compared with experimental data here. Although the experimental data for a hydrophobic surface corroborated the computational and theoretical data, the case of a superhydrophobic surface showed the bubbles to be able to contain significantly larger volumes than predicted. This is attributed to the greater ability of the bubble contact line to advance compared with its tendency to detach from the surface because of buoyancy. We surmise that a static model therefore describes only an unstable equilibrium for these bubbles, which unless heavily isolated from external influences are more likely to assume a larger stable size.

Phenytoin (Dilantin) and acupuncture therapy in the treatment of intractable oral and facial pain.

Phenytoin is an anti-convulsant and anti-arrhythmic medication. Manufactured by various pharmaceutical companies with various brand names, phenytoin (PHT) is also known as Dilantain, Hydantoin or Phenytek in the United States; Dilantain or Remytoine in Canada; Epamin, Hidantoina in Mexico; and Fenidatoin or Fenitron or other names elsewhere in the world. Phenytoin (PHT) is especially useful for patients suffering from intractable oral and facial pain especially those who exhibit anger, stress, depression and irrational emotions commonly seen in the patients with oral and facial pain. When used properly, Phenytoin is also an effective anxiolysis drug in addition to its theraputic effects on pain and can be used alone or, even better, if combined with other compatible sedatives. Phenytoin is particularly valuable when combined with acupuncture for patients with trigeminal neuralgia, glossopharyneal neuralgia, Bell's palsy, and some other facial paralysis and pain. It also has an advantage of keeping the patient relatively lucid after treatment. Either PHT or acupuncture alone can benefit patients but the success of treatment outcome may be limited. We found by combining both acupuncture and PHT with Selective Drug Uptake Enhancement by stimulating middle finger at the first segment of ventral (palmar) and lateral surfaces, as well as prescribing PHT with the dosage predetermined for each patient by Bi-Digital O-Ring Test (BDORT), the treatment outcome was much better resulted with less recurrence and intensity of pain during episodes of attack. Patients with Bell's palsy were most benefited by acupuncture therapy that could completely get rid of the illness.

Clinical effectiveness of acupuncture for mandibular subluxation and dislocation.

Dislocation or subluxation of mandible could occur suddenly without Patient's awareness of its forthcoming. Patient may discover suddenly during yawning, laughing, or when the mouth is wide open that he or she could not close the jaw. It may cause serve anxiety and apprehension, that may put the patient in such a nervous state that may worsen the condition, and also may spastically tense the muscles associated with dislocation. We treated 37 patients in the past and found that, although five patients could be manipulated to have their dislocated jaw reduced to the normal state, we found that a majority of the cases could not be manipulated without supplementing with other adjunctive methods such as acupuncture at the pertinent acupoints, or injections of local anesthetic around the temporomandibular joint area. Twenty-seven patients were successful to have the dislocation or subluxation reduced, five patients required local anesthetic for reduction and 1 patient had to have the reduction done in the operating room under deep sedation. We found acupuncture is valuable in reducing the mandibular subluxation and dislocation. Three acupoints in calming down the patients were a valuable aid during treatment. LI 4 which is known to reduce pain in head and neck region could increase pain threshold and decrease anxiety associated with discomfort encountered during reduction treatment. Additional acupoints such as P 6 (Neikuan), Ext 1 (Yintang), and H 7 (Shenmen) are valuable for the patients who are tense and nervous. Those acupoints are also could be utilizied as additional aid to ease the spasm of the muscles associated with subluxation and dislocation. Post-operative care includes stabilization at the head and neck region.

Comparing the clinical effect of five varying locations of LI.4 acupoint.

LI.4 is a major acupoint but the method of locating it has not been standardized. In fact, description of method for locating this acupoint often varies in the classic and traditional texts. It might signify this point may be varied from one to another person. Our comparative study of locating and subsequent acupuncturing these locations revealed some interesting features of LI.4 from our collected clinical data in that location 1 had a better therapeutic effect for toothache relief and analgesia-anesthesia effect than for headache relief, location 2 was better for headache than toothache relief; locations 3 and 4 had a mixed effect whereas, location 5 seems to have a better chance to get bioenergy (De Qi) as manifested by tingling and numbing sensation at the acupunctured site. Our study also suggested that LI.4 location was about the size of 4 millimeters in diameter instead of a pin-point location, though needle inserted at correct point produced a better result.

Anxiety control of dental patients by clinical combination of acupuncture, Bi-Digital O-Ring Test, and eye movement desensitization with sedation via submucosal route.

The data presented in this article was collected after reviewing clinical findings gathered from using various anxiety control methods on apprehensive patients. We examined clinical applications of the eye movement (EM) component of Eye Movement Desensitization (EMD) on fearful dental patients who have histories of traumatic dental experiences. We also used Bi-Digital O-Ring Test (BDORT) to select the proper dosage of sedative to minimize the adverse side effects. For patients who did not respond well to EM, we used BDORT to select the proper sedative medication and its dosage. In certain difficult cases, we supplemented these techniques with acupuncture to augment the sedative effects. Findings were based on the clinical impressions and assessments of both the patients and the operating team. Results showed that EM, although effective in enabling patients to undergo non-invasive dental procedures such as clinical examination and simple prophylaxis, had only limited beneficial effect with invasive procedures such as extraction, drilling, and injections, etc. We also found that BDORT greatly reduced adverse side effects of sedatives such as hypertension, hypotension, hypoxia, tachycardia, bradycardia, nausea, and vomiting. For most apprehensive patients, we found that EMD and acupuncture combined with BDORT predetermined dosage for the submucosal sedation enabled these patients to undergo the complete dental treatment. The authors try to explain the mechanism of BDORT and EM in terms of visual awareness (or consciousness) and preferred patterns, where neurons in the brain respond to the actions and/or direction of movement. The authors believe that BDORT and EM could have better results if the persons performing BDORT have visual awareness and are focused on the task; whereas in EM, the patient's eye on the therapist's hand movements. A more focused approach via visual pathway will result in more favorable results in EM. Likewise, performing BDORT absentmindedly could lead to false results if visual awareness (or consciousness) is absent. "Preferred pattern" will arouse neurons in the brain to cause conscientiousness, and performing BDORT with 'open eyes' arouse the necessary visual awareness that is necessary for the successful performance of BDORT tasks.

Anatomical relevance of some acupuncture points in the head and neck region that dictate medical or dental application depending on depth of needle insertion.

Many of the acupuncture points on the face, according to classic acupuncture textbooks, could be used to treat facial pain, paralysis, and toothache. But it is not specified which acupuncture point would be effective for which tooth. Many of these points, when used for the treatment of dental pain, often fail. From an anatomical point of view, we describe which acupuncture point to use for each specific area for effective treatment of dental pain. Also, we emphasize the importance of the depth of needle insertion, especially the necessity to touch the facial bone, for effective pain treatment. When performed properly, acupuncture can be very effective for relief of dental pain.

Managing acute withdrawal syndrome on patients with heroin and morphine addiction by acupuncture therapy.

Though there are articles and case reports about using acupuncture to detoxify and to break the narcotic addiction, few articles describe in the West about using acupuncture therapy to treat the emergence of acute withdrawal symptom due to heroin, opium, or morphine. Most often the method of treatment are using the methadone or benzodiazepine and phenoziazine drugs this article describes many years of clinical experience with non-drug approach to treat the acute withdrawal symptoms with acupuncture therapy. Unlike the drug approach, which usually has side effects, there is no adverse effect with acupuncture therapy.

Transplanting supersites of HIV-1 vulnerability.

One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite.

A comparison of the clinical effectiveness of various acupuncture points in reducing anxiety to facilitate hypnotic induction.

This study determined if any acupuncture point (acupoint) known for its calming effects also aided hypnotic induction. Hypnosis was offered to 108 patients requiring minor surgical or dental procedures. All had a history of panic attacks and surgical or dental phobias that complicated or prevented treatment. Unpleasant intruding thoughts of imminent invasive treatments handicapped their ability to accept hypnotic induction; however, acupuncture therapy was proposed to the consenting patient to facilitate hypnotic induction and augment its effects. Each patient received one selected acupoint for acupuncture therapy. Of the 6 acupoints used (LI 4, H 7, SP 6, P 6, GV 24, and Ext-hn-21), GV 24 was best at enhancing hypnotic induction whereas LI 4 produced the best muscular relaxation and P 6 for reducing tension.

An Historical Review and Perspective on the Impact of Acupuncture on U.S. Medicine and Society.

BACKGROUND: It took almost 300 years for Europe and 400 years for the United States to finally appreciate the therapeutic value of acupuncture. Findings from basic medical research that acupuncture stimulation causes release of endorphins, serotonin, enkephalins, and γ-amino-butyric acid (GABA; a major inhibitory neurotransmitter of the brain), norepinephrine, and dopamine helped to explain the acupuncture effect on a biomedical and pharmacological basis that was acceptable to the Western medical establishment. CONTEXT: In the United States, there is significantly increased familiarity with acupuncture and U.S. patients have sought acupuncture treatment to relieve stress-related syndromes, to enhance the immune system, to reduce insomnia, to improve athletic performance, and to address Alzheimer's disease, as well as for cardiac and poststroke therapy. This article briefly reviews the history of acupuncture in the United States and discusses the potential of this modality in the the future. DISCUSSION: Acupuncture can be combined with conventional Western medicine for pain management in patient with cancer to reduce dosages of narcotic medications, side-effects, adverse reactions, and the possibility of narcotic addiction. Because of acupuncture's increased popularity, acupuncture training schools have been set up in the United States, and some insurance companies cover acupuncture therapy. CONCLUSIONS: By studying both Eastern and Western medicine and using them in a complementary fashion, we open ourselves to many discoveries for the benefit of humanity.

N332-Directed broadly neutralizing antibodies use diverse modes of HIV-1 recognition: inferences from heavy-light chain complementation of function.

Dozens of broadly neutralizing HIV-1 antibodies have been isolated in the last few years from the sera of HIV-1-infected individuals. Only a limited number of regions on the HIV-1 spike, however, are recognized by these antibodies. One of these regions (N332) is characterized by an N-linked glycan at residue 332 on HIV-1 gp120 and is recognized by antibody 2G12 and by the recently reported antibodies PGT121-137, the latter isolated from three donors. To investigate the diversity in mode of antibody recognition at the N332 site, we used functional complementation between antibody heavy and light chains as a means of assessing similarity in mode of recognition. We examined a matrix of 12 PGT-heavy chains with each of 12 PGT-light chains. Expression in 96-well format for the 144 antibodies (132 chimeric and 12 wild-type) was generally consistent (58 ± 10 µg/ml). In contrast, recognition of HIV-1 gp120 was bimodal: when the source of heavy and light chains was from the same donor, recognition was good; when sources of heavy and light chains were from different donors, recognition was poor. Moreover, neutralization of HIV-1 strains SF162.LS and TRO.11 generally followed patterns of gp120 recognition. These results are consistent with published sequence, mutational, and structural findings, all of which indicate that N332-directed neutralizing antibodies from different donors utilize different modes of recognition, and provide support for a correlation between functional complementation of antibody heavy and light chains and similarity in antibody mode of recognition. Overall, our results add to the growing body of evidence that the human immune system is capable of recognizing the N332-region of HIV-1 gp120 in diverse ways.

Effect of tetracaine-induced spinal anesthesia on pial microcirculation in pentobarbital anesthetized rats.

Local anesthetic is administrated intrathecally to produce spinal anesthesia. This study examines the effect of spinal anesthesia induced by intrathecal tetracaine on cerebral pial microcirculation in rats. We monitored changes in the mean arterial pressure, internal diameter (ID) of the pial arteriole, intracranial pressure, and red blood cell velocity. The regional cerebral blood flow was calculated from the product of cross sectional area and red blood cell velocity. To induce spinal anesthesia, tetracaine was administered via a polyethylene tube at the L4-5 intervertebral space after laminectomy. Arterial blood pressure was monitored via a catheter in the femoral artery. A left parietal craniotomy with an encapsulated cranial window was prepared for biomicroscopy. Change in the arteriolar ID was measured by image shearing. Red blood cell velocity was measured by the dual-slit photometric method and correlation technique. Three levels of spinal anesthesia were evaluated. Tetracaine at 0.1 and 0.2 mg/kg, which produced T10 and T6 sensory block, respectively, did not cause significant change of ID of the pial arteriole and red blood cell velocity. Tetracaine (0.3 mg/kg) produced total spinal block, resulting in a significant decrease of the calculated cerebral blood flow and caused brief pial arteriolar vasodilation followed by vasoconstriction. Our results show that total spinal anesthesia with tetracaine causes significant changes in rat cerebral microcirculation.