Deep Brain Stimulation Improves Symptoms of Spasmodic Dysphonia Through Targeting of Thalamic Sensorimotor Connectivity.

BACKGROUND AND OBJECTIVES: Spasmodic dysphonia is a dystonia of the vocal chords producing difficulty with speech. Current hypotheses are that this is a condition of dysregulated thalamic sensory motor integration. A recent randomized controlled trial of thalamic deep brain stimulation (DBS) demonstrated its safety and efficacy. Our objective was to determine whether the outcome could be predicted by stimulation of thalamic sensorimotor areas and adjacent white matter connectivity as assessed by diffusion tractography. METHODS: A cohort of 6 participants undergoing thalamic DBS for adductor spasmodic dysphonia was studied. Electrodes were localized with the Lead-DBS toolbox. Group-based analyses were performed with atlases, coordinates, and using voxel-based symptom mapping. Diffusion tensor imaging (3 T, 64 directions, 2-mm isotropic) was used to perform individual probabilistic tractography (cerebellothalamic tract and pallidothalamic tract) and segmentation of the thalamus. Monopolar review was performed at 0.5 V and binarised as effective or ineffective. RESULTS: Effective contacts stimulated more of thalamic sensorimotor areas than ineffective contacts (P < .05, false discovery rate corrected). This effect was consistent across analytical and statistical techniques. Group-level and tractography analyses did not identify a specific "sweet spot" suggesting the benefit of DBS is derived from modulating individual thalamic sensorimotor areas. Stimulations at 1 year involved predicted thalamic sensorimotor regions with additional cerebellothalamic tract involvement. CONCLUSION: Stimulation of thalamic sensorimotor areas was associated with improvement in symptoms of spasmodic dysphonia. These data are consistent with DBS acting on pathophysiologically dysregulated thalamic sensorimotor integration in spasmodic dysphonia.

Mydriasis and anisocoria in a pediatric hyperhidrosis patient with interesting findings in the family cat.

Here, we report a case of unilateral ocular mydriasis in a pediatric patient with longstanding hyperhidrosis, as well as similar findings in her cat. The patient had been undergoing treatment of her hyperhidrosis with topical glycopyrrolate. This case highlights the potential side effect profile of topical antimuscarinics and the importance of counseling patients on proper precautions.

Electrocardiogram Signals Denoising Using Improved Variational Mode Decomposition.

BACKGROUND: Electrocardiogram (ECG) plays a vital role in the analysis of heart activity. It can be used to analyze the different heart diseases and mental stress assessment also. Various noises, such as baseline wandering, muscle artifacts and power line interface disturbs the information within the ECG signal. To acquire correct information from ECG signal, these noises should be removed. METHODS: In the proposed work, the improved variational mode decomposition (IVMD) method for the removal of noise in ECG signals is used. In the proposed method, the weighted signal amplitude integrated over the timeframe of the ECG signal varies the window size during decomposition. Raw ECG data are extracted from 10 subjects and ECG data are also taken from the MIT BIH database for the proposed method. RESULTS: The performance comparison of traditional variational mode decomposition (VMD) and the proposed technique is also calculated using mean square error, percentage root mean square difference, signal to noise ratio and correlation coefficient. The extracted highest signal to noise ratio (SNR) value of acquired ECG signals using traditional VMD is 42db whereas highest value of signal to noise ratio (SNR) using improved VMD (IVMD) is 83db. CONCLUSION: The proposed IVMD technique represented better performance than traditional VMD for denoising of ECG signals.

A rational diagnostic approach to the "phantom hCG" and other clinical scenarios in which a patient is thought to be pregnant but is not.

The scenario in which a patient tests positive for human chorionic gonadotropin (hCG) in the absence of pregnancy can pose a diagnostic dilemma for clinicians. The term "phantom hCG" refers to persistently positive hCG levels on diagnostic testing in a nonpregnant patient and such results often lead to a false diagnosis of malignancy and subsequent inappropriate treatment with chemotherapy or hysterectomy. There remains a need for a consistent and rational diagnostic approach to the "phantom hCG." This article aims to review the different etiologies of positive serum hCG testing in nonpregnant subjects and concludes with a practical, stepwise diagnostic approach to assist clinicians encountering this clinical dilemma.

Situs Ambiguous Anomaly during Laparoscopic Cholecystectomy in an Adult Female.

Situs anomalies are rare structural defects affecting 0.01% of general population. They present with multisystem structural defects mostly involving cardiovascular, respiratory and GI systems. Situs abnormality with presence of multiple spleen is termed as left atrial isomerism with anatomical and structural differences to its countertype situs ambiguous with asplenia (right atrial isomerism). In this case report, we present an adult case of situs ambiguous anomaly which was diagnosed incidentally during laparoscopic cholecystectomy. The patient had enlarged left lobe of liver, multiple splenules on right side, malrotated small and large gut, interrupted inferior vena cava with azygos continuation, and bilateral bilobed lungs. It is concluded that variations in situs ambiguous cases differ and a single description is not possible. It is crucial to reveal these variations by using imaging modalities and being aware of them prior to surgery and invasive intervention to prevents the possible risks and complications.

Detection of unamplified target genes via CRISPR-Cas9 immobilized on a graphene field-effect transistor.

Most methods for the detection of nucleic acids require many reagents and expensive and bulky instrumentation. Here, we report the development and testing of a graphene-based field-effect transistor that uses clustered regularly interspaced short palindromic repeats (CRISPR) technology to enable the digital detection of a target sequence within intact genomic material. Termed CRISPR-Chip, the biosensor uses the gene-targeting capacity of catalytically deactivated CRISPR-associated protein 9 (Cas9) complexed with a specific single-guide RNA and immobilized on the transistor to yield a label-free nucleic-acid-testing device whose output signal can be measured with a simple handheld reader. We used CRISPR-Chip to analyse DNA samples collected from HEK293T cell lines expressing blue fluorescent protein, and clinical samples of DNA with two distinct mutations at exons commonly deleted in individuals with Duchenne muscular dystrophy. In the presence of genomic DNA containing the target gene, CRISPR-Chip generates, within 15 min, with a sensitivity of 1.7 fM and without the need for amplification, a significant enhancement in output signal relative to samples lacking the target sequence. CRISPR-Chip expands the applications of CRISPR-Cas9 technology to the on-chip electrical detection of nucleic acids.

Graphene-based biosensor for on-chip detection of bio-orthogonally labeled proteins to identify the circulating biomarkers of aging during heterochronic parabiosis.

Studies of heterochronic parabiosis, where two animals of different ages are joined surgically, provided proof-of-principle results that systemic proteins have broad age-specific effects on tissue health and repair. In an effort to identify these systemic proteins, we previously developed a method to selectively label the proteome of only one animal joined in parabiosis utilizing bio-orthogonal non-canonical amino acid tagging (BONCAT), which can metabolically label proteins during their de novo synthesis by incorporating a methionine substitute, azido-nor-leucine (ANL), in cells expressing a mutant methionyl-tRNA synthetase (MetRSL274G). Once labeled, we can selectively identify the proteins produced by the MetRSL274G transgenic mouse in the setting of heterochronic parabiosis. This approach enabled the detection of several rejuvenating protein candidates from the young parabiont, which were transferred to the old mammalian tissue through their shared circulation. Although BONCAT is a very powerful technology, the challenges associated with its complexity including large starting material requirements and cost of ANL-labeled protein detection, such as modified antibody arrays and mass spectrometry, limit its application. Herein, we propose a lab-on-a-chip technology, termed Click-A+Chip for facile and rapid digital detection of ANL-labeled proteomes present in minute amount of sample, to replace conventional assays. Click-A+Chip is a graphene-based field effect biosensor (gFEB) which utilizes novel on-chip click-chemistry to specifically bind to ANL-labeled biomolecules. In this study, Click-A+Chip is utilized for the capture of ANL-labeled proteins transferred from young to old parabiotic mouse partners. Moreover, we were able to identify the young-derived ANL-labeled Lif-1 and leptin in parabiotic systemic milieu, confirming previous data as well as providing novel findings on the relative levels of these factors in young versus old parabionts. Summarily, our results demonstrate that Click-A+Chip can be used for rapid detection and identification of ANL-labeled proteins, significantly reducing the sample size, complexity, cost and time associated with BONCAT analysis.

Epidermoid Cyst in Inguinal Canal: A Rare Presentation.

The patients presenting with lump in inguinal area are mostly suspected as hernias. Epidermoid cyst commonly presenting in head and neck region rarely may develop from inguinal canal structures. We present here a rare case of epidermoid cyst measuring 7×8 cm as a content of inguinal canal diagnosed by ultrasonography. Surgical excision was done and confirmed as epidermoid cyst by histopathology. We conclude that cutaneous cysts in inguinal area may be a presentation and should be kept in mind for differential diagnosis.

Bilateral Giant Juvenile Fibroadenoma of Breast.

Fibroadenomas are benign lesions of breast commonly found in young age group. These focal tumours contain both mesenchymal and glandular tissue. Giant juvenile fibroma of breast is rare variant of fibroadenoma found usually in less than 20 years of age. They present with rapid enlargement of single or multiple, discrete, painless large nodule of breast. A 14-years-old premenarche girl presented with large bilateral breast lumps for two months. FNAC showed features of juvenile fibroadenoma. Breast conserving surgical excision of lumps was performed and histopathology confirmed the diagnosis of juvenile fibroadenoma. Giant juvenile fibroadenomas are characterised by rapid enlargement of encapsulated mass. The aetiology is unknown, although end-organ hypersensitivity to normal level of estrogen is postulated. We present a case of bilateral giant juvenile fibroadenoma for its rarity.

Topographic anatomy of the great auricular point: landmarks for its localization and classification.

PURPOSE: The great auricular point (GAP) marks the exit of the great auricular nerve at the posterior border of the sternocleidomastoid muscle (SCM). It is a key landmark for the identification of the spinal accessory nerve, and its intraoperative localization is vital to avoid neurological sequelae. This study delineates the topography and surface anatomy landmarks that used to localize the GAP. METHODS: Thirty cadaveric heminecks were dissected on a layer-by-layer approach. The topography of the GAP was examined relative to the insertion point of the SCM at the clavicle, tip of the mastoid process, and angle of the mandible. The GAP and its relation to the SCM were determined as a ratio of the total length of the SCM. RESULTS: The GAP was demonstrated to be in a predictable location. The mean length of the SCM was 131.4 ± 22 mm, and the mean distance between the GAP and the mastoid process was found to be 60.4 ± 13.76 mm. The ratio of the GAP location to the total SCM length ranged between 0.33-0.57. The mean distance between the angle of the mandible and the GAP was determined to be 57 ± 22.2 mm. Based on the midpoint of the SCM, the GAP was above it in 66.7 % of subjects and classified to Type A, and below it in 33.3 % of subjects appointed to Type B. CONCLUSIONS: The anatomical landmarks utilized in this study are helpful in predicting the location of the GAP relative to the midpoint of the SCM and can reduce neural injuries within the posterior triangle of the neck.

Assessment of Severity of Peritonitis Using Mannheim Peritonitis Index.

INTRODUCTION: Peritonitis is one of the most common problems in general surgery practice with high mortality rate. One of the reasons for high mortality is that peritonitis affects the general condition and leads to complications causing multiple organ failure, renal failure, sepsis, and postoperative ventilatory support. Early prognostic evaluation of patients with peritonitis is desirable to select high-risk patients for intensive management and also to provide a reliable objective classification of severity and operative risk. PATIENTS AND METHODS: Fifty cases with diagnosis of peritonitis coming to Government Medical College, Amritsar, were studied. Stratification of these patients was done according to Mannheim peritonitis index (MPI), and their outcome was examined. RESULTS: Mortality steadily increases with increase in MPI score. For patients with a score <21, the mortality rate was 0%; for score 21-27, it was 27.28%; and for score >27, it was 100% (P < 0.001). For patients with a score <21, the morbidity rate was 13.33%; for score 21-27, it was 65.71%; and for score >27, it was 100% (P < 0.001). Duration of pain >24 h, organ failure on admission, female sex, and feculent exudate were found to be independently significant factors in predicting the mortality among the study population. For a score of 27, the sensitivity was 66.67%, specificity was 100%, and positive predictive value for mortality is 100% at an accuracy of 94%. CONCLUSION: This study proves that MPI scoring system is a simple and effective tool for assessing the morbidity and mortality in patients with peritonitis.

Unilateral pallidal deep brain stimulation in a patient with dystonia secondary to episodic ataxia type 2.

BACKGROUND/AIMS: This paper describes the use of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in the treatment of secondary dystonia caused by expisodic ataxia type 2 (EA2). METHODS: We present the case of a patient with EA2, an autosomal dominant condition, who developed late-onset cervical and right upper limb segmental dystonia. The patient underwent left GPi DBS. RESULTS: Within 4 months of commencing stimulation of the left GPi, the patient had resolution of his neck pain and was able to keep the head straighter for longer time intervals. There was also improvement in right arm segmental dystonia. There was an improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS 21.5) of 55% at 4 months and of 51% at 22 months. CONCLUSION: The treatment of secondary dystonia is difficult and the results with GPi DBS are less favourable compared with primary dystonia. This case illustrates the successful treatment of secondary dystonia caused by EA2.

Rechargeable internal neural stimulators--is there a problem with efficacy?

INTRODUCTION: With the advent of rechargeable internal neural stimulators (rINS) for deep brain stimulation, our aim was to survey patient satisfaction and clinical efficacy in an early cohort of patients receiving this new technology. METHODS: This is an observational study on nine patients with rINS. All patients had initially received non-rechargeable INS with established efficacy of their deep brain stimulation system for either dystonia or pain. Patient satisfaction and efficacy with their rINS were established by completion of a questionnaire, a quality of life assessment (SF-36), and calculation of the total electrical energy delivered (TEED) by the rINS. RESULTS: A reduction in efficacy of their rINS was noticed in 22% of patients. In 78% of patients, there was a problem with recharging their rINS because of poor contact. Two patients (22%) felt that recharging the rINS interfered with their lives and it was a daily reminder that they had a deep brain stimulator system in situ. Eight out of nine patients (89%), however, would recommend to other patients to have an rINS. CONCLUSION: Most patients were happy with their rechargeable internal neural stimulator. A reduction in efficacy was noticed in 22% of patients, which is similar to the proportion of patients noticing a reduction in efficacy when replacing with a non-rechargeable system. Thus, all patients require close monitoring post-replacement of rINS, in case possible adjustment of parameters is required.

Endogenous high-performance liquid chromatography/tandem mass spectrometry interferences and the case of perfluorohexane sulfonate (PFHxS) in human serum; are we overestimating exposure?

Perfluorinated acids have received increasing scientific attention due to their widespread global distribution, environmental persistence and bioaccumulation in wildlife and humans. For perfluorohexane sulfonate (PFHxS, C(6)F(13)SO(3) (-), m/z 399), all existing human data have been generated using high-performance liquid chromatography (HPLC) and its most sensitive tandem mass spectrometric (MS/MS) transitions (m/z 399/80 [SO(3)](-) or m/z 399/99 [SO(3)F](-)), but this may be problematic because of co-eluting endogenous steroid sulfates that share common fragmentation pathways. We examined the magnitude of over-reporting for PFHxS in pregnant women (n = 29), and in pooled serum of males, non-pregnant and pregnant females (n = 3, 100 samples per pool), by comparing m/z 399/80 and 399/99 data with an interference-free transition, m/z 399/119. PFHxS concentrations in pregnant women determined using m/z 399/80 and 399/99 (p < 0.05), but not m/z 399/119, were positively correlated to the response of the steroid sulfates. This led to an average overestimation of PFHxS by 1.5- and 4.7-fold, using m/z 399/80 and 399/99, respectively, and validated the use of m/z 399/119 for the first time. The interferences were a problem in all human serum samples, and analysis of pooled serum revealed statistically significant over-reporting by m/z 399/80 and 399/99 for pregnant women > non-pregnant women > men. The magnitude of over-reporting here represents a worst-case scenario, but the extent to which the published literature values are biased is unknown due to limited details of methods in existing reports. Instead of using the less sensitive m/z 399/119 transition, we showed that an alternative selection of column and mobile phase can allow for sufficient chromatographic separation of the interferences. In conclusion, it was shown that routine analytical methods are prone to systematically overestimating PFHxS concentrations in serum of men or women, but that this can be avoided by alternative chromatographic steps or MS/MS transitions.