Using Optogenetics to Model Cellular Effects of Alzheimer's Disease.

Across the world a dementia case is diagnosed every three seconds. Alzheimer's disease (AD) causes 50-60% of these cases. The most prominent theory for AD correlates the deposition of amyloid beta (Aß) with the onset of dementia. Whether Aß is causative remains unclear due to findings such as the recently approved drug Aducanumab showing effective clearance of Aß, but not improving cognition. New approaches for understanding Aß function, are therefore necessary. Here we discuss the application of optogenetic techniques to gain insight into AD. Optogenetics, or genetically encoded, light-dependent on/off switches, provides precise spatiotemporal control to regulate cellular dynamics. This precise control over protein expression and oligomerization or aggregation could provide a better understanding of the etiology of AD.

Condensation of the Drosophila nerve cord is oscillatory and depends on coordinated mechanical interactions.

During development, organs reach precise shapes and sizes. Organ morphology is not always obtained through growth; a classic counterexample is the condensation of the nervous system during Drosophila embryogenesis. The mechanics underlying such condensation remain poorly understood. Here, we characterize the condensation of the embryonic ventral nerve cord (VNC) at both subcellular and tissue scales. This analysis reveals that condensation is not a unidirectional continuous process but instead occurs through oscillatory contractions. The VNC mechanical properties spatially and temporally vary, and forces along its longitudinal axis are spatially heterogeneous. We demonstrate that the process of VNC condensation is dependent on the coordinated mechanical activities of neurons and glia. These outcomes are consistent with a viscoelastic model of condensation, which incorporates time delays and effective frictional interactions. In summary, we have defined the progressive mechanics driving VNC condensation, providing insights into how a highly viscous tissue can autonomously change shape and size.

Mechanics of epidermal morphogenesis in the Drosophila pupa.

Adult epidermal development in Drosophila showcases a striking balance between en masse spreading of the developing adult precursor tissues and retraction of the degenerating larval epidermis. The adult precursor tissues, driven by both intrinsic plasticity and extrinsic mechanical cues, shape the segments of the adult epidermis and appendages. Here, we review the tissue architectural changes that occur during epidermal morphogenesis in the Drosophila pupa, with a particular emphasis on the underlying mechanical principles. We highlight recent developments in our understanding of adult epidermal morphogenesis. We further discuss the forces that drive these morphogenetic events and finally outline open questions and challenges.

Scaling of internal organs during Drosophila embryonic development.

Many species show a diverse range of sizes; for example, domestic dogs have large variation in body mass. Yet, the internal structure of the organism remains similar, i.e., the system scales to organism size. Drosophila melanogaster has been a powerful model system for exploring scaling mechanisms. In the early embryo, gene expression boundaries scale very precisely to embryo length. Later in development, the adult wings grow with remarkable symmetry and scale well with animal size. Yet, our knowledge of whether internal organs initially scale to embryo size remains largely unknown. Here, we utilize artificially small Drosophila embryos to explore how three critical internal organs-the heart, hindgut, and ventral nerve cord (VNC)-adapt to changes in embryo morphology. We find that the heart scales precisely with embryo length. Intriguingly, reduction in cardiac cell length, rather than number, appears to be important in controlling heart length. The hindgut, which is the first chiral organ to form, displays scaling with embryo size under large-scale changes in the artificially smaller embryos but shows few hallmarks of scaling within wild-type size variation. Finally, the VNC only displays weak scaling behavior; even large changes in embryo geometry result in only small shifts in VNC length. This suggests that the VNC may have an intrinsic minimal length that is largely independent of embryo length. Overall, our work shows that internal organs can adapt to embryo size changes in Drosophila, but the extent to which they scale varies significantly between organs.

Evaluation of Changes in the Pharyngeal Airway Space as a Sequele to Mandibular Advancement Surgery: A Cephalometric Study.

PURPOSE: To evaluate effect of mandibular advancement on pharyngeal airway space using lateral cephalogram. MATERIALS AND METHODS: Twenty patients who were diagnosed with class II skeletal malocclusion and underwent surgical intervention for the correction of their dentofacial deformity following orthodontic treatment were included. The soft tissue changes in the pharyngeal space were brought about by the surgical intervention, and the changes that had occurred in increasing the airway were evaluated by using cephalogram. RESULTS: The results of this study showed that following mandibular advancement surgery, the pharyngeal airway space increased along with an increase in the length and thickness of the uvula with a reduction in the angulation. All the changes remained stable in the late postoperative phase. CONCLUSION: Patients who underwent mandibular advancement showed a significant increase in the pharyngeal airway space and that remained stable during the evaluation period. As a consequence, mandibular advancement seems to be the most stable surgical movement in relation to airway dimensional gains.

Multiple radiolucencies in the mandible: A diagnostic dilemma.

Diagnosis and treatment planning of maxillofacial pathologies is an art. It requires careful evaluation and correlation of clinical presentation and radiologic investigations. When the pathology concerned is an intraosseous lesion, the radiographic findings assume a significantly more important role. While carrying out the radiographic assessment, we rely on typical findings regarding the number, location, and appearance of radiolucent areas which point towards certain types of pathologies. Whenever these findings are atypical or at variance with the clinical presentation, it creates a diagnostic dilemma for the clinician. We report a case of a 34-year-old man who presented with a simple clinical history but multiple radiolucencies on the radiograph.

Metabolic response to maxillofacial trauma revisited: A retrospective study.

PURPOSE: Management of a trauma patient aims at stabilization or resuscitation and revival from critical condition resulting from various sequences of systemic pathophysiological responses in the body. Hematological changes are the first signs reflecting the homeostasis mechanisms starting in the body after injury. The aim of the current study is to evaluate the physiological changes following maxillofacial trauma and extrapolate the findings to understand the posttrauma responses. PATIENTS AND METHOD: This is a retrospective study involving 192 subjects divided into two groups, trauma group and control group. In both the groups, baseline vitals and complete blood picture were recorded for comparison. In trauma group, the recordings were made within 24 h after maxillofacial injury. RESULTS: All the parameters were analyzed using SPSS version 18. Independent sample t-test was used to assess the nature of data distribution and statistical significance was considered only at P value < 0.05. On comparison of complete blood picture mean values of hemoglobin (13.63 vs 12.18), RBC count (4.51 vs 4.10), WBC count (8835.48 vs 8336.56) were seen to be higher in trauma patients compared to control subjects. The mean bleeding times are almost equal (2.35 vs 2.47) but the clotting times (5.42 vs 5.26), random blood glucose (94.78 vs 90.13), and blood urea (27.14 vs 26.30) were marginally higher in trauma group but were statistically insignificant. The mean value of serum creatinine (0.84 vs 0.80) was comparatively higher in trauma patients and was statistically significant. Study of vitals revealed that mean systolic blood pressures were almost equal (120.65 vs 121.08) in both the groups. The mean diastolic blood pressures (79.46 vs 88.49) and oxygen saturation (93.73 vs 98.86) in trauma patients are comparatively reduced. The mean values of temperature (99.30 vs 98.50) and pulse rate (102.38 vs 97.14) were on relatively higher side in trauma group compared with control group. SUMMARY AND CONCLUSION: Using basic blood parameters and vitals in the present study, the compensatory mechanisms happening in the body after maxillofacial trauma can be seen. These changes although significant on side by side comparison can still fall within the normal physiological range provided by various diagnostic setups. Hence, the need for maxillofacial surgeon to be sensitive to minor variations in these aspects to ensure safety of the patient cannot be overemphasized.

Dynamic Stability Assessment of the Temporomandibular Joint as a Sequela of Open Reduction and Internal Fixation of Unilateral Condylar Fracture.

PURPOSE: Dynamic stability of the temporomandibular joint (TMJ) is the characteristic of the joint to achieve normal function by harmonious, balanced, synchronized interactions of the various functional subunits of the stomatognathic system. The aim of this study was to evaluate changes in the mechanics and dynamics of the TMJ during recovery from surgical treatment of an isolated condylar fracture. PATIENTS AND METHODS: This is a prospective cohort study involving 30 patients who underwent open reduction and internal fixation for an isolated unilateral condylar fracture and were clinically asymptomatic at 6 months after surgery. The dynamics of the TMJ were assessed by bite-force analysis, both static and dynamic, to assess masticatory efficiency. Surface electromyography was recorded to assess changes in muscle dynamics. Joint vibration analysis was performed to evaluate the internal functioning of the TMJ. All the assessments were carried out bilaterally to allow comparison of the injured and uninjured joints, and the data were analyzed with the paired t test and independent-samples t test. Statistical significance was considered at P < .05. RESULTS: The study included 18 male and 12 female patients aged between 20 and 40 years. Bite-force analyses showed significantly higher bite forces on the uninjured side at 6 months after surgery. Similarly, surface electromyography analysis showed increased muscle activity on the affected side pointing toward some compensatory hyperactivity in the masticatory muscles. Joint vibration analysis showed that there was increased friction during function in both the injured and uninjured joints. CONCLUSIONS: The observations in this study suggest that residual imbalances are present in the TMJ at 6 months after open reduction and internal fixation of condylar fractures. Therefore, long-term studies are required to establish a complete timeline of adaptive changes occurring in the TMJ after condylar fractures, especially in comparison with other treatment modalities.

Pre-emptive Diclofenac Versus Ketoprofen as a Transdermal Drug Delivery System: How They Face.

AIM: To compare the analgesic efficacy of Diclofenac vis-a-vis Ketoprofen transdermal patch, in the management of immediate post-operative pain following orthognathic procedures. MATERIAL AND METHOD: A prospective, double-blinded, randomised controlled study was conducted among 50 subjects, between 2012 and 2015. These patients were diagnosed clinically and cephalometrically as skeletal and dental class II malocclusion and underwent bi-jaw surgical procedure. In total, 25 Diclofenac and 25 Ketoprofen transdermal patches, sealed in envelopes and numbered, were administered to subjects. The patches used, contained 100 mg of either Diclofenac or Ketoprofen and administered by a nurse prior to induction. Duration of analgesia, severity of pain using Visual Analog Scale, necessity of rescue analgesia (spontaneous pain > 5 on a 10-cm scale) and any other adverse effect associated with the drug were evaluated. RESULTS: Mean duration of analgesia was significantly higher in the Ketoprofen group (20 h), compared to Diclofenac group (13 h) (p = 0.001). Rescue analgesia was required in 12% of subjects who received Diclofenac patch, compared to 4% in Ketoprofen group. None of the subjects showed any allergic reactions. CONCLUSION: The study was designed to evaluate the efficacy of transdermal patch in reduction of post-operative pain in subjects undergoing bi-jaw surgeries. Subjects in both groups were comfortable and returned to early function. However, Ketoprofen transdermal patch had an edge over the Diclofenac transdermal patch with respect to analgesic efficacy.

Comparison of Efficacy of Halstead, Vazirani Akinosi and Gow Gates Techniques for Mandibular Anesthesia.

PURPOSE: Traditionally, the "Halstead block" has been widely used to provide anesthesia in mandibular teeth. Two other techniques, the Gow Gates mandibular nerve block and the Akinosi Vazirani closed-mouth mandibular nerve block, are reliable alternatives to the conventional inferior alveolar nerve block. The purpose of this study is to evaluate the onset of anesthesia, anesthetic success and incidence of positive aspiration during administration of local anesthetic solution using the Halstead, Vazirani Akinosi and Gow Gates techniques. MATERIALS AND METHOD: The study involves 210 subjects, divided into three different groups of 70 subjects each receiving Gow Gates, Vazirani Akinosi and conventional inferior alveolar nerve blocks. The onset of anesthesia, positive aspiration and anesthetic success was evaluated. RESULTS: In Vazirani Akinosi technique group, patients showed highest anesthetic success of 95.71%; there was a significant difference seen between the Gow Gates and Vazirani Akinosi techniques (p = 0.0241*). The mean value of the onset of anesthesia in Gow Gates technique showed the longest 343.71 ± 153.20 s, in Halstead technique it was 177.43 ± 59.94 s, and in Vazirani Akinosi technique it was 192.86 ± 61.20 s. There was a significant difference seen between Gow Gates and Vazirani Akinosi techniques (p = 0.0001*) and Gow Gates and inferior alveolar nerve block techniques (p = 0.0001*). CONCLUSION: The Vazirani Akinosi technique was found to be significantly better than the other two techniques with respect to both onset and success of anesthesia. Positive aspirations were slightly higher in the conventional IANB technique compared to the other two, but did not reach statistical significance.

Musculoskeletal Changes as a Sequel to Advancement Genioplasty: A Long-Term Cephalometric Prospective Study.

AIMS: The aim of this study was to evaluate cephalometrically the stability of hard tissues and soft tissue changes of advancement genioplasty 2 years after surgery. METHODS: A prospective study was conducted which comprised of 25 patients, who underwent advancement genioplasty alone with no other orthognathic surgical procedures. Immediate pre-operative, 6 months postoperative, and 2 years postoperative lateral cephalograms were compiled and assessed. RESULTS: The mean surgical advancement planned was around 8 mm. Six months post-surgery, the relapse rate was 15% of the surgical advancement which was considerably reduced in the following 18 months to 7%. The ratio of soft tissue to bony advancement at pogonion was 0.9:1. There are significant alterations in the soft tissue profile in terms of decrease in the soft tissue thickness, facial convexity angle, deepened mentolabial sulcus and minimal increase in the lower lip height. CONCLUSION: Advancement genioplasty was considered as a relatively stable procedure, if adequate muscular pedicle and internal rigid fixation were maintained. The present study was of 2 years, and we can expect further changes in the hard and soft tissues, which are clinically irrelevant.

Time trend of neurocysticercosis in children with seizures in a tertiary hospital of western Nepal.

INTRODUCTION: Neurocysticercosis is a common cause of seizure disorders in children of Western Nepal. The clinical presentation is variable. The incidence varies depending on the food habits and ethnicity of the population. The present study was undertaken with the objective of studying the mode of presentation, radiological findings and to determine the recent trend of the disease in children of Western Nepal. METHODS: Records from the Department of Pediatrics, Manipal Teaching Hospital, Pokhara, Nepal of children aged 0-17 years admitted from 2003 to 2015 and with the discharge diagnosis of seizure and neurocysticercosis (NCC) were reviewed. The diagnosis was primarily based on clinical features, neurological involvement and CT and MRI studies. Seizures due to other CNS pathologies were excluded. Patients with NCC were treated with Albendazole15mg/kg/day for 28 days with supportive treatments for seizures and raised intracranial pressure. Patients were followed up for one year after the completion of the treatment. RESULTS: There were 1355 cases of seizure disorders, out of which 229 (16.90%) were NCC. There were 99 (43.23%) in the age group 6-10 years followed by 91 (41.09%) in the age group of 11-15 years. Seizures were the most common presenting symptom in 88.65%, followed by raised ICP in 9.61%. Neuropsychiatric changes were noted in 38 cases (16.59%). CT scan findings revealed single lesion in 78.16% and multiple lesions in 21.83%. Poisson regression analysis showed statistically significant decline of year-wise incidence of NCC cases (p<0.05) from 2003 to 2015. CONCLUSION: The decline in the incidence of NCC in recent years is most probably attributed to improved hygiene with the construction of household toilets to avoid open defecation and biannual deworming with Albendazole as a part of School Health and Nutrition Project.

A Tendon Cell Specific RNAi Screen Reveals Novel Candidates Essential for Muscle Tendon Interaction.

Tendons are fibrous connective tissue which connect muscles to the skeletal elements thus acting as passive transmitters of force during locomotion and provide appropriate body posture. Tendon-derived cues, albeit poorly understood, are necessary for proper muscle guidance and attachment during development. In the present study, we used dorsal longitudinal muscles of Drosophila and their tendon attachment sites to unravel the molecular nature of interactions between muscles and tendons. We performed a genetic screen using RNAi-mediated knockdown in tendon cells to find out molecular players involved in the formation and maintenance of myotendinous junction and found 21 candidates out of 2507 RNAi lines screened. Of these, 19 were novel molecules in context of myotendinous system. Integrin-ßPS and Talin, picked as candidates in this screen, are known to play important role in the cell-cell interaction and myotendinous junction formation validating our screen. We have found candidates with enzymatic function, transcription activity, cell adhesion, protein folding and intracellular transport function. Tango1, an ER exit protein involved in collagen secretion was identified as a candidate molecule involved in the formation of myotendinous junction. Tango1 knockdown was found to affect development of muscle attachment sites and formation of myotendinous junction. Tango1 was also found to be involved in secretion of Viking (Collagen type IV) and BM-40 from hemocytes and fat cells.

Comparative evaluation of a herbal mouthwash (Freshol) with chlorhexidine on plaque accumulation, gingival inflammation, and salivary Streptococcus mutans growth.

INTRODUCTION: Plaque accumulation and oral microorganisms are the main predisposing factors to various orodental infections and targeting these, therefore, can prove to be an effective way of combating these diseases. Herbal extracts have been of particular interest these days owing to various side effects associated with conventional modes of treatment. AIMS AND OBJECTIVES: The present study was conducted to compare the efficacy of a commercially available homeopathic mouthwash with chlorhexidine on plaque status, gingival status, and salivary Streptococcus mutans count. MATERIALS AND METHODS: Total sample of 55 children, aged 8-14 years, were randomly divided into two groups. Group A (35) and Group B (20) were given 10 mL of test mouthwash "Freshol" and chlorhexidine respectively during phases 1 and 3 of the clinical trial which was of 10 days each. Phase 2 of 14 days in between was the washout period during which no mouthwash was given. RESULT: Freshol was found to be better than chlorhexidine in reducing the salivary mutans streptococci count and equieffective to chlorhexidine in altering plaque and gingival scores. CONCLUSION: Herbal alternatives can prove to be an effective and safe alternative to conventional modes of treatment.

Right-sided hemiagenesis of the thyroid lobe and isthmus: A case report.

Unilateral or bilateral hypoplasia or agenesis of one or both thyroid lobes, with or without isthmic agenesis, is a rare developmental anomaly. Hemiagenesis of the left lobe is far commoner than of the right. Clinically, these patients may be euthyroid, hyperthyroid, or hypothyroid. Ultrasonography is usually able to diagnose this condition easily, as we demonstrate in this case report of a 37-year-old lady with an incidentally detected thyroid nodule who was found to have hemiagenesis of the right lobe and isthmus.