Role of Sialendoscopy in Non-neoplastic Parotid Diseases: A Prospective Study of 241 Patients in Indian Population.

Objectives: To assess the role of sialendoscopy as a diagnostic modality and in managing cases of non-neoplastic parotid gland diseases. Secondly, to provide descriptive analysis of intraoperative findings. Methods: The patients of chronic parotid sialadenitis who presented with complaints of recurrent unilateral or bilateral parotid swelling and pain were included in the study. All patients underwent sialendoscopy, and the findings were noted. Intervention was carried out in the same sitting like dilatation of stenosis, stone removal by basket, combined approach, flushing of mucoid flakes, etc. Failed cases were worked up with radiological investigation and managed accordingly. Results: Two hundred and forty-one cases of parotid sialadenitis who underwent sialendoscopy between 2012 and 2018 were included. Diagnostic sialendoscopy was achieved in 100% cases, while intervention was successful in 96.7% (233/241) cases after the first procedure. On diagnostic sialendoscopy, ductal stenosis was the most common pathology present in 177 (73.4%) patients followed by stones (12%) and debris (11.6%). All cases of stenosis were serially dilated with increasing sizes of sialendoscopes followed by stenting in 75% of the cases. The diagnosis of juvenile recurrent parotitis was confirmed in 17 children (mean age 5.6 years) with consistent clinical history and sialendoscopic findings of stenosis along with pale ductal mucosa. There were 18 cases where ductal perforation was seen. One case showed multiple hyperdense foci in bilateral parotid gland along with multiple strictures that underwent repeat sialendoscopy, but the symptoms did not resolve, and finally the patient underwent bilateral superficial parotidectomy. Conclusion: Sialendoscopy is a safe and highly effective modality in managing non-neoplastic parotid gland disorders with low complication rates and resulted in gland preservation in the vast majority of patients. Therefore, it can be concluded that sialendoscopy is the diagnostic and therapeutic modality of choice for parotid obstructive sialadenitis.

Once-Daily vs. Twice-Daily Administration of Inhaled Budesonide for Mild and Moderate Well-Controlled Childhood Asthma: A Randomized, Controlled Trial.

OBJECTIVES: To compare median change in morning peak expiratory flow rate (PEFR) and clinical asthma control in children receiving total daily dosage of inhaled budesonide administered either as once-daily or divided twice-daily dose. METHODS: It was a randomized, parallel group, open label, noninferiority trial on 80 children aged 5-12 y with mild or moderate well-controlled asthma. Baseline parameters were recorded and subjects received inhaled budesonide either as once-daily or divided twice-daily dose. Primary outcome was median change in morning PEFR. Secondary outcomes included median change in evening and diurnal variation in PEFR, asthma symptom control as per Global Initiative for Asthma, 2017 and Asthma Control Questionnaire, and spirometric measurements taken at the clinic. RESULTS: The median [interquartile range (IQR)] increase in morning PEFR was more in children receiving once-daily as compared to those receiving twice-daily inhaled budesonide (by 6:00 L/min; IQR: -44.00-63.00 L/min vs. 4:00 L/min; IQR: -67.50-67.50 L/min, p 0.222; 95% CI: -1.37 to 19.08). Other spirometric variables and symptoms scores were also nonsignificant except median change in evening PEFR which was in favor of twice-daily regimen. CONCLUSION: Once-daily administration of inhaled budesonide is noninferior to twice-daily administration of equivalent daily dosage of inhaled budesonide.

Structural and binding studies of cyclin-dependent kinase 2 with NU6140 inhibitor.

Cyclin-dependent kinase 2 (CDK2) is an established target protein for therapeutic intervention in various diseases, including cancer. Reported inhibitors of CDK2 target the ATP-binding pocket to inhibit the kinase activity. Many small molecule CDK2 inhibitors have been discovered, and their crystal structure with CDK2 or CDK2-cyclin A complex has been published. NU6140 is a CDK2 inhibitor with moderate potency and selectivity. Herein, we report the cocrystal structure determination of NU6140 in complex with CDK2 and confirmation of the binding using various biophysical methods. Our data show that NU6140 binds to CDK2 with a Kd of 800 nM as determined by SPR and stabilizes the protein against thermal denaturation (ΔTm -5°C). The cocrystal structure determined in our study shows that NU6140 binds in the ATP-binding pocket as expected for this class of compounds and interacts with Leu83 and Glu81 with regular hydrogen bonds and with Asp145 via water-mediated H-bond. Based on these data, we propose structural modifications of NU6140 to introduce new interactions with CDK2 that can improve its potency while retaining the selectivity.

Combined Endoscopic-Transcutaneous Approach for Management of Large Parotid Stones.

INTRODUCTION: The aim of this paper is to present our experience with combined endoscopic-transcutaneous approach in terms of effectiveness and safety in patients with large or impacted parotid stones. MATERIALS AND METHODS: This is a prospective study carried out from August, 2012 to February, 2017 analyzing 21 patients with parotid sialolithiasis. The indication of combined approach was either failed attempt to remove the stone endoscopically, large size (>4mm), or impacted stone. The exact location of the stone was pointed out by endoscopic transillumination and the stone was removed via transcutaneous incision which could be linear incision or a preauricular incision followed by stenting for 3 weeks. RESULTS: We were successfully able to remove the stone in all 21 cases using modified Blair's incision in 18 cases, while a linear incision was used in remaining 3 cases. Two patients developed stricture in the post-operative period at 5 and 3 months, respectively. The strictures were successfully dilated endoscopically and the patients are asymptomatic ever since. CONCLUSION: Combined endoscopic-transcutaneous approach is a highly successful approach with few complications for removal of parotid stones and thus resulting in high gland preservation rates in patients of parotid sialolithiasis.

IgG4-Related Diseases-Continues To Be a Cancer Mimicker.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic multisystem immune-mediated disease. Histologically, it presents as infiltration with IgG4-secreting plasma cells affecting many organs such as the pancreas, lacrimal glands, salivary glands, kidneys, and arteries, resulting in chronic fibrosis and scarring within the tissue which over time forms into a mass. It is a slow-growing process that usually remains indolent until it causes a mass effect or tissue infiltration. Our patient was found to have a pancreatic mass on imaging concerning pancreatic neoplastic lesions. He subsequently underwent biopsy for histology/pathology and IgG4 levels, which led to our diagnosis of IgG4-RD. Imaging, blood tests, and, most importantly, histopathological features of the involved organ are important in determining the diagnosis. This is important as a treatment plan will be based on the given diagnosis, and patients with IgG4-RD respond very well to systemic steroid therapy.

Cerebral Venous Sinus Thrombosis with Bilateral Abducens Palsy in a Patient with Heterozygous Prothrombin G20210A Mutation.

We present a rare case of cerebral venous thrombosis in a patient with heterozygous mutation of the prothrombin G20210A gene. A 24-year-old Caucasian male complained of sudden onset diplopia due to bilateral abducens palsy and throbbing headache with pulsatile tinnitus. Computed tomography revealed extensive thrombus in the right sigmoid sinus, right transverse sinus, and the superior sagittal sinus. Except for the prothrombin mutation, no other predisposing risk factors were found. The patient was treated with heparin, later transitioned to enoxaparin and warfarin, and subsequently, the symptoms improved on follow-up. This case reveals the rare occurrence of cerebral venous thrombosis in a patient having prothrombin gene G20210A mutation alone. Early diagnosis and treatment can lead to a good prognosis.

18p Deletion Syndrome: Case Report with Clinical Consideration and Management.

18p deletion syndrome is characterized by the deletion of short arm of chromosome 18. Presentation of this syndrome is quite variable with dysmorphic features, growth deficiencies, and mental retardation with poor verbal performance. Few patients even fail to thrive when malformations involving the heart and brain are severe. In the present article, we report an isolated case of 18p deletion in a 23-year-old female who for the first time reported to the hospital for dental problems. The patient was short statured with mental retardation and craniofacial, skeletal, dental, and endocrinal abnormalities. Such presentation warrants prompt diagnosis for effective management. Furthermore, genetic counseling for such patients and their families should be considered as a part of treatment itself.

GroEL-GroES assisted folding of multiple recombinant proteins simultaneously over-expressed in Escherichia coli.

Folding of aggregation prone recombinant proteins through co-expression of chaperonin GroEL and GroES has been a popular practice in the effort to optimize preparation of functional protein in Escherichia coli. Considering the demand for functional recombinant protein products, it is desirable to apply the chaperone assisted protein folding strategy for enhancing the yield of properly folded protein. Toward the same direction, it is also worth attempting folding of multiple recombinant proteins simultaneously over-expressed in E. coli through the assistance of co-expressed GroEL-ES. The genesis of this thinking was originated from the fact that cellular GroEL and GroES assist in the folding of several endogenous proteins expressed in the bacterial cell. Here we present the experimental findings from our study on co-expressed GroEL-GroES assisted folding of simultaneously over-expressed proteins maltodextrin glucosidase (MalZ) and yeast mitochondrial aconitase (mAco). Both proteins mentioned here are relatively larger and aggregation prone, mostly form inclusion bodies, and undergo GroEL-ES assisted folding in E. coli cells during over-expression. It has been reported that the relative yield of properly folded functional forms of MalZ and mAco with the exogenous GroEL-ES assistance were comparable with the results when these proteins were overexpressed alone. This observation is quite promising and highlights the fact that GroEL and GroES can assist in the folding of multiple substrate proteins simultaneously when over-expressed in E. coli. This method might be a potential tool for enhanced production of multiple functional recombinant proteins simultaneously in E. coli.

Osteochondroma of maxilla posterior region: a unique case.

Osteochondroma is the most common benign neoplasm of the skeleton commonly affecting the long bones due to endochondral growth. In the craniofacial region this tumour is very rare. The sites of predilection are the coronoid process and the mandibular condyle. Here, we report an exceptional case of osteochondroma originating from the maxillary posterior region in a 26-year-old male patient, mimicking an odontome, not reported earlier in the literature. We also discuss the importance of various imaging modalities, most importantly, computed tomography (CT) in the evaluation of such lesions. However, histopathology remains the mainstay for definitive diagnosis in such conditions.

Irreversible denaturation of maltodextrin glucosidase studied by differential scanning calorimetry, circular dichroism, and turbidity measurements.

Thermal denaturation of Escherichia coli maltodextrin glucosidase was studied by differential scanning calorimetry, circular dichroism (230 nm), and UV-absorption measurements (340 nm), which were respectively used to monitor heat absorption, conformational unfolding, and the production of solution turbidity. The denaturation was irreversible, and the thermal transition recorded at scan rates of 0.5-1.5 K/min was significantly scan-rate dependent, indicating that the thermal denaturation was kinetically controlled. The absence of a protein-concentration effect on the thermal transition indicated that the denaturation was rate-limited by a mono-molecular process. From the analysis of the calorimetric thermograms, a one-step irreversible model well represented the thermal denaturation of the protein. The calorimetrically observed thermal transitions showed excellent coincidence with the turbidity transitions monitored by UV-absorption as well as with the unfolding transitions monitored by circular dichroism. The thermal denaturation of the protein was thus rate-limited by conformational unfolding, which was followed by a rapid irreversible formation of aggregates that produced the solution turbidity. It is thus important to note that the absence of the protein-concentration effect on the irreversible thermal denaturation does not necessarily means the absence of protein aggregation itself. The turbidity measurements together with differential scanning calorimetry in the irreversible thermal denaturation of the protein provided a very effective approach for understanding the mechanisms of the irreversible denaturation. The Arrhenius-equation parameters obtained from analysis of the thermal denaturation were compared with those of other proteins that have been reported to show the one-step irreversible thermal denaturation. Maltodextrin glucosidase had sufficiently high kinetic stability with a half-life of 68 days at a physiological temperature (37°C).

Are frontal sinuses useful indicators of sex?

Accurate sex prediction of skeletonised human remains excludes one-half of the population, enabling a more focussed search of missing persons' files. The skull is useful in sex assessment of skeletonised remains; however, its fragmentation precludes the use of all conventional craniofacial markers. The frontal bone may be recovered intact in fragmented remains and the sinuses therein may be useful in sex differentiation. A total of 100 paranasal sinus view radiographs of 50 males and females each were evaluated for potential differences in frontal sinus configuration following the methods of Yoshino et al. (Forensic Sci Int 1987; 34:289-99.) and Tang et al. (Forensic Sci Int 2009; 183:104.e1-3.). Data were assessed through univariate and multivariate statistics. The univariate Mann-Whitney U-test revealed statistically insignificant sexual dimorphism (p > 0.05) for the frontal sinuses. Moreover, multivariate logistic regression equations allowed correct sex identification in 60% of cases only. Possible reasons for the low sexual dimorphism may be frontal sinus' high inter-individual variability; also, existing techniques that employ frontal sinus classification systems may lead to a loss of information when features that require visual observation are grouped and assigned class numbers. The results herein suggest that frontal sinuses may have limited application as the sole predictor of sex.