Van Eerdewegh P, Little RD, Dupuis J, et al Nature 2002;418:426–430 

To identify novel genetic polymorphisms associated with bronchial hyperresponsiveness (BHR) in asthma

Four hundred sixty white affected sib-pair families from the United States and the United Kingdom with current asthma

A genetic linkage analysis was performed for current asthma and BHR Case-control, transmission disequilibrium, and haplotype analyses were conducted to identify the gene(s) most commonly associated with asthma Novel genes of interest were …

Association of the adam33 gene with asthma and bronchial hyperresponsiveness

In the golden age of pharmaceutical nanocarriers, we are witnessing a maturation stage of the original concepts and ideas. There is no doubt that nanoformulations are extremely valuable tools for drug delivery applications; the current challenge is how to optimize them to ensure that they are safe, effective and scalable, so that they can be manufactured at an industrial level and advance to clinical use. In this context, lipid nanoparticles have gained ground, since they are generally regarded as non-toxic, biocompatible and easy-to-produce formulations. Pharmaceutical applications of lipid nanocarriers are a burgeoning field for the transport and delivery of a diversity of therapeutic agents, from biotechnological products to small drug molecules. This review starts with a brief overview of the characteristics of solid lipid nanoparticles and discusses the relevancy of performing systematic preformulation studies. The main applications, as well as the advantages that this type of nanovehicles offers in certain therapeutic scenarios are discussed. Next, pharmacokinetic aspects are described, such as routes of administration, absorption after oral administration, distribution in the organism (including brain penetration) and elimination processes. Safety and toxicity issues are also addressed. Our work presents an original point of view, addressing the biopharmaceutical aspects of these nanovehicles by means of descriptive statistics of the state-of-the-art of solid lipid nanoparticles research. All the presented results, trends, graphs and discussions are based in a systematic (and reproducible) bibliographic search that considered only original papers in the subject, covering a 7 years range (2013-today), a period that accounts for more than 60% of the total number of publications in the topic in the main bibliographic databases and search engines. Focus was placed on the therapeutic fields of application, absorption and distribution processes and current efforts for the translation into the clinical practice of lipid-based nanoparticles. For this, the currently active clinical trials on lipid nanoparticles were reviewed, with a brief discussion on what achievements or milestones are still to be reached, as a way of understanding the reasons for the scarce number of solid lipid nanoparticles undergoing clinical trials.

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Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects

Genomewide Association Studies of Stroke

This report was written by the Japanese Society of Dysphagia Rehabilitation, the Japanese Association of Rehabilitation Nutrition, the Japanese Association on Sarcopenia and Frailty, and the Society of Swallowing and Dysphagia of Japan to consolidate the currently available evidence on the topics of sarcopenia and dysphagia. Histologically, the swallowing muscles are of different embryological origin from somatic muscles, and receive constant input stimulation from the respiratory center. Although the swallowing muscles are striated, their characteristics are different from those of skeletal muscles. The swallowing muscles are inevitably affected by malnutrition and disuse; accumulating evidence is available regarding the influence of malnutrition on the swallowing muscles. Sarcopenic dysphagia is defined as dysphagia caused by sarcopenia of the whole body and swallowing-related muscles. When sarcopenia does not exist in the entire body, the term "sarcopenic dysphagia" should not be used. Additionally, sarcopenia due to neuromuscular diseases should be excluded; however, aging and secondary sarcopenia after inactivity, malnutrition and disease (wasting disorder and cachexia) are included in sarcopenic dysphagia. The treatment of dysphagia due to sarcopenia requires both dysphagia rehabilitation, such as resistance training of the swallowing muscles and nutritional intervention. However, the fundamental issue of how dysphagia caused by sarcopenia of the swallowing muscles should be diagnosed remains unresolved. Furthermore, whether dysphagia can be caused by primary sarcopenia should be clarified. Additionally, more discussion is required on issues such as the relationship between dysphagia and secondary sarcopenia, as well as the diagnostic criteria and means for diagnosing dysphagia caused by sarcopenia. Geriatr Gerontol Int 2019; 19: 91-97.

Sarcopenia and dysphagia: Position paper by four professional organizations.

Background
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews, 2005, Issue 4 (and last updated in the Cochrane Database of Systematic Reviews, 2013 issue 8), on local anaesthetic blockade (LASB) of the sympathetic chain to treat people with complex regional pain syndrome (CRPS).

Objectives
To assess the efficacy of LASB for the treatment of pain in CRPS and to evaluate the incidence of adverse effects of the procedure.

Search methods
For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 9), MEDLINE (Ovid), EMBASE (Ovid), LILACS (Birme), conference abstracts of the World Congresses of the International Association for the Study of Pain, and various clinical trial registers up to September 2015. We also searched bibliographies from retrieved articles for additional studies.

Selection criteria
We considered randomised controlled trials (RCTs) that evaluated the effect of sympathetic blockade with local anaesthetics in children or adults with CRPS compared to placebo, no treatment, or alternative treatments.

Data collection and analysis
We used standard methodological procedures expected by Cochrane. The outcomes of interest were reduction in pain intensity, the proportion who achieved moderate or substantial pain relief, the duration of pain relief, and the presence of adverse effects in each treatment arm. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.

Main results
We included an additional four studies (N = 154) in this update. For this update, we excluded studies that did not follow up patients for more than 48 hours. As a result, we excluded four studies from the previous review in this update. Overall we included 12 studies (N = 461), all of which we judged to be at high or unclear risk of bias. Overall, the quality of evidence was low to very low, downgraded due to limitations, inconsistency, imprecision, indirectness, or a combination of these.

Two small studies compared LASB to placebo/sham (N = 32). They did not demonstrate significant short-term benefit for LASB for pain intensity (moderate quality evidence).

One small study (N = 36) at high risk of bias compared thoracic sympathetic block with corticosteroid and local anaesthetic versus injection of the same agents into the subcutaneous space, reporting statistically significant and clinically important differences in pain intensity at one-year follow-up but not at short term follow-up (very low quality evidence).

Of two studies that investigated LASB as an addition to rehabilitation treatment, the only study that reported pain outcomes demonstrated no additional benefit from LASB (very low quality evidence).

Eight small randomised studies compared sympathetic blockade to various other active interventions. Most studies found no difference in pain outcomes between sympathetic block versus other active treatments (low to very low quality evidence).

One small study compared ultrasound-guided LASB with non-guided LASB and found no clinically important difference in pain outcomes (very low quality evidence).

Six studies reported adverse events, all with minor effects reported.

Authors' conclusions
This update's results are similar to the previous versions of this systematic review, and the main conclusions are unchanged. There remains a scarcity of published evidence and a lack of high quality evidence to support or refute the use of local anaesthetic sympathetic blockade for CRPS. From the existing evidence, it is not possible to draw firm conclusions regarding the efficacy or safety of this intervention, but the limited data available do not suggest that LASB is effective for reducing pain in CRPS.

/pdf/local-anaesthetic-sympathetic-blockade-for-complex-regional-4v1jqnjpk8.pdf

Local anaesthetic sympathetic blockade for complex regional pain syndrome

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.

/pdf/preparation-and-evaluation-of-tacrolimus-loaded-322swuem7x.pdf

Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution.

Objective
To evaluate the relationships between tongue pressure and different aspects of the oral-phase swallowing function.

/pdf/the-relationship-between-tongue-pressure-and-oral-dysphagia-1m8re74xt5.pdf

The Relationship Between Tongue Pressure and Oral Dysphagia in Stroke Patients

Importance Identification of the factors associated with improved facial nerve function after treatment of Bell palsy is important to provide patients with early and effective treatment. Objective To identify factors that are associated with improved treatment outcomes in patients with Bell palsy. Design, Setting, and Participants This retrospective cohort study included 1364 patients with Bell palsy treated at the outpatient clinic of the Department of Otolaryngology at the Kyung Hee University Hospital, Seoul, Republic of Korea, between January 1, 2005, and December 31, 2017. The medical records of patients admitted to this hospital for management of acute facial palsy were reviewed by 3 otolaryngologists with more than 20 years’ experience in treating facial palsy. Main Outcomes and Measures Facial function at the initial and final visits were measured using the House-Brackmann (H-B) grading system, which is one of several analysis tools developed to quantify facial function and provide reproducible information. It is a widely accepted system for grading facial function in 6 steps, from normal (H-B grade I) to total paralysis (H-B grade VI). Results In total, 1364 patients with primary Bell palsy (718 [52.6%] women) and a mean (SD) age of 47.7 (16.7) years were enrolled. The overall rate of favorable outcome, which was defined as an H-B grade of I or II at the 6-month follow-up visit, was 80.6% (1099 of 1364 patients). Of 1099 patients who had a favorable outcome at 6 months, 343 (31.2%) were younger than 40 years. Of 1364 patients, 1053 (77.2%) had moderate facial dysfunction (H-B grade III or IV). No pathological spontaneous fibrillation activity (ie, good electromyography [EMG] results) was detected on EMG in 937 of 1364 patients (68.7%), 492 (36.1%) had controlled hypertension, and 673 (49.3%) were treated with oral corticosteroids alone. Multivariable analysis revealed that the following factors were associated with favorable outcome: age younger than 40 years (odds ratio [OR], 1.56; 95% CI, 1.09-2.22), an initial H-B grade of III or IV (OR, 2.62; 95% CI, 1.93-3.57), good EMG results after 2 weeks of treatment (OR, 3.38; 95% CI, 2.48-4.61), absence of diabetes (OR, 1.43; 95% CI, 1.04-2.36), and control of hypertension (OR, 1.64; 95% CI, 1.16-2.33). Conclusions and Relevance Multiple logistic regression analysis in this study suggests that multiple clinical factors are associated with favorable outcomes in patients with Bell palsy.

Evaluation of Factors Associated With Favorable Outcomes in Adults With Bell Palsy

Objective To evaluate the association between baseline characteristics, three physical performance tests and fall history in a sample of the elderly from Korean population. Methods A total of 307 participants (mean age, 76.70±4.85 years) were categorized into one of two groups, i.e., fallers and non-fallers. Fifty-two participants who had reported falling unexpectedly at least once in the previous 12 months were assigned to the fallers group. Physical performance tests included Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS), Timed Up and Go test. The differences between the two study groups were compared and we analyzed the correlations between fall histories and physical performance tests. Results SPPB demonstrated a significant association with fall history. Although the BBS total scores did not show statistical significance, two dynamic balance test items of BBS (B12 and B13) showed a significant association among fallers. Conclusion This study suggests that SPPB and two dynamic balance test items of the BBS can be used in screening for risk of falls in an ambulatory elderly population.

/pdf/the-association-between-fall-history-and-physical-124r8szfiz.pdf

The Association Between Fall History and Physical Performance Tests in the Community-Dwelling Elderly: A Cross-Sectional Analysis.

Monomelic amyotrophy (MMA), also known as Hirayama disease, is a sporadic juvenile muscular atrophy in the distal upper extremities. This disorder rarely involves proximal upper extremities and presents minimal sensory symptoms with no upper motor neuron (UMN) signs. It is caused by anterior displacement of the posterior dural sac and compression of the cervical cord during neck flexion. An 18-year-old boy visited our clinic with a 5-year history of left upper extremity pain and slowly progressive weakness affecting the left shoulder. Atrophy was present in the left supraspinatus and infraspinatus. On neurological examination, positive UMN signs were evident in both upper and lower extremities. Electrodiagnostic study showed root lesion involving the fifth to seventh cervical segment of the cord with chronic and ongoing denervation in the fifth and sixth cervical segment innervated muscles. Cervical magnetic resonance imaging (MRI) showed asymmetric cord atrophy apparent in the left side and intramedullary high signal intensity along the fourth to sixth cervical vertebral levels. With neck flexion, cervical MRI revealed anterior displacement of posterior dural sac, which results in the cord compression of those segments. The mechanisms of myelopathy in our patient seem to be same as that of MMA. We report a MMA patient involving proximal limb with UMN signs in biomechanical concerns and discuss clinical importance of cervical MRI with neck flexion. The case highlights that clinical variation might cause misdiagnosis.

/pdf/monomelic-amyotrophy-hirayama-disease-with-upper-motor-1cl7996v5m.pdf

Jinmann Chon

Papers

Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution.

The Relationship Between Tongue Pressure and Oral Dysphagia in Stroke Patients

Evaluation of Factors Associated With Favorable Outcomes in Adults With Bell Palsy

The Association Between Fall History and Physical Performance Tests in the Community-Dwelling Elderly: A Cross-Sectional Analysis.

Monomelic Amyotrophy (Hirayama Disease) With Upper Motor Neuron Signs: A Case Report