Cadaveric Study of Crista Fenestra: Revisited.

OBJECTIVES: Since there is great confusion in the literature about the anatomy and terms of the crista fenestra (CF) and the crista semilunaris, this paper is confined to the anatomy of the inferior margin of the round window (RW). METHODS: This study was carried out on 20 cadaveric temporal bones. We measured the maximal height of the RW and the maximum height of the inferior bony edge of the RW, (termed CF type A), in this study. The ratio of the maximum height of CF type A to the maximum height of the RW was calculated. After drilling the CF type A, the scala tympani was visualized using a sialendoscope, and any bony projection in the inferior wall of the scala tympani just behind the round window membrane (RWM) was assessed and reported (termed CF B in this study). RESULTS: We identified CF type A in 19/20 of cases (95%), and it was absent in only 1 case (5%). Its height ranged from 0.228 to 1.329 mm with an average of 0.604±0.347 mm. The percentage of CF type A to RW ranged from 19 to 75%, with an average of 42%. CF type B was present in only 2 specimens (10%). CONCLUSION: CF type A occupied a significant part of the RW in most specimens, and therefore its drilling was essential in a large percentage of cases. CF type B (inside the scala tympani) was present in 10% of the temporal bone samples, and curettage had to be done in these cases.

Synthesis of Triphenylphosphonium Phospholipid Conjugates for the Preparation of Mitochondriotropic Liposomes.

Surface modification of liposomes with a ligand is facilitated by the conjugation of the ligand to a hydrophobic molecule that serves to anchor the ligand to the liposomal bilayer. We describe here a simple protocol to conjugate a triphenylphosphonium group to several commercially available functionalized phospholipids. The resulting triphenylphosphonium-conjugated lipids can be used to prepare liposomes that preferentially associate with mitochondria when exposed to live mammalian cells in culture.

The Anatomy and Anatomical Variations of the Round Window Prechamber and Their Implications on Cochlear Implantation: An Anatomical, Imaging, and Surgical Study

Abstract Introduction Over the last decades, there has been a tremendous increase in the number of cochlear implant recipients and, consequently, there is a recent increase of interest in the proper understanding of the anatomy of the round window (RW), which is the most important anatomical land mark during cochlear implant surgery. Objectives The present study was undertaken to assess the detailed surgical and radiological anatomy of the RW prechamber; its shape, directions, measurements, common anatomic variations, and its relationships with different surrounding structures as related to cochlear implantation. Methods A total of 20 cadaveric specimens of human temporal bone were microscopically dissected for the anatomical assessment of the measurements of the RW and its relation to surrounding structures in the tympanum. A total of 20 patients were subjected to cochlear implantation, and a radiological and surgical assessment of the anatomy of their RW prechambers was performed. Results The distances between the RW and the facial canal (FC), the jugular fossa (JF), the carotid canal (CC), and the oval window (OW) were measured. Among the cases subjected to cochlear implantation, the infracochlear tunnel was studied radiologically; the lengths of the anterior and posterior pillars were assessed, and the relation with the direction at which the RW faces was statistically analyzed. Conclusions Proper understanding of the topographic anatomy of the RW, including its direction of opening and the distances from different adjacent structures in the tympanum, is essential for a successful cochlear implantation surgery, since it can help decision-making before the surgery and is useful to avoid many complications, such as misplaced electrode and iatrogenic injury to the surrounding structures.

The Anatomy and Anatomical Variations of the Round Window Prechamber and Their Implications on Cochlear Implantation: An Anatomical, Imaging, and Surgical Study.

Introduction Over the last decades, there has been a tremendous increase in the number of cochlear implant recipients and, consequently, there is a recent increase of interest in the proper understanding of the anatomy of the round window (RW), which is the most important anatomical land mark during cochlear implant surgery. Objectives The present study was undertaken to assess the detailed surgical and radiological anatomy of the RW prechamber; its shape, directions, measurements, common anatomic variations, and its relationships with different surrounding structures as related to cochlear implantation. Methods A total of 20 cadaveric specimens of human temporal bone were microscopically dissected for the anatomical assessment of the measurements of the RW and its relation to surrounding structures in the tympanum. A total of 20 patients were subjected to cochlear implantation, and a radiological and surgical assessment of the anatomy of their RW prechambers was performed. Results The distances between the RW and the facial canal (FC), the jugular fossa (JF), the carotid canal (CC), and the oval window (OW) were measured. Among the cases subjected to cochlear implantation, the infracochlear tunnel was studied radiologically; the lengths of the anterior and posterior pillars were assessed, and the relation with the direction at which the RW faces was statistically analyzed. Conclusions Proper understanding of the topographic anatomy of the RW, including its direction of opening and the distances from different adjacent structures in the tympanum, is essential for a successful cochlear implantation surgery, since it can help decision-making before the surgery and is useful to avoid many complications, such as misplaced electrode and iatrogenic injury to the surrounding structures.

Validation and adaptation of the Arabic version of the Tonsil and Adenoid Health Status Instrument.

OBJECTIVES: Validation and cross-cultural adaptation of the Tonsil and Adenoid Health Status study tool, in Arabic while studying its psychometric properties. STUDY DESIGN: prospective -validation study. SETTINGS: Multiple tertiary centers. PATIENTS/AND OTHER PARTICIPANTS: 63 consecutive patients who underwent tonsillectomy or adenotonsillectomy operation (pre-operative and 6 months post-operative) and 65 asymptomatic controls. INTERVENTION/METHODS: FOLLOWING: Guidelines for the cross-cultural adaptation process, to translate the original English language version into an Arabic language one. MAIN OUTCOME MEASURES: We assessed the psychometric properties of the Arabic version of the TAHSI (A-TAHSI) its feasibility, reproducibility, internal consistency, reliability, discriminatory validity and responsiveness to change. RESULTS: The Mann-Whitney test showed a statistically significant difference for the mean score between the patients and the control group denoting good clinical validity. The Cronbach's coefficient value for the A- TAHSI for 63 cases was 0.983, demonstrating good internal consistency. The Wilcoxon signed-rank test showed a marked improvement in the patients' scores 6 months post-operatively. Spearman's rank and Pearson's correlations were used to correlate the level of resemblance of the mean score of the A-TAHSI, which showed statistically significant results. CONCLUSIONS: The A-TAHSI is a valid instrument for evaluating the subjective effect of tonsillectomy on the health and quality of life and hence is recommended to be used in tonsillectomy research and daily practice. LEVEL OF EVIDENCE: 3b.

Laparoscopic Sleeve Gastrectomy Versus Laparoscopic Roux-en-Y Gastric Bypass in Elderly Bariatric Patients: Safety and Efficacy-a Systematic Review and Meta-analysis.

INTRODUCTION: Obesity is a chronic disease due to excess fat storage, a genetic predisposition, and environmental contribution where surgery offers a viable treatment option. The surgical treatment of obesity in the elderly population (> 55 years) remains controversial. PURPOSE: To evaluate the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in elderly bariatric patients. MATERIALS AND METHODS: Data was sourced from MEDLINE, EMBASE, CINAHL, PubMed, and Cochrane databases for peer-reviewed, randomized controlled trials, and observational studies in the English language were searched from the year 1991 until 2019. From the extracted data, early and late procedural complications and mortality were used as safety outcomes. Weight loss was the primary outcome for effectiveness while the resolution of obesity-related comorbidities was included as secondary outcomes. The Review Manager (Rev Man 5.3)™ software was used for statistical analysis. RESULTS: Of the forty-one screened studies, nine studies were included in the final analysis. There was no difference between LSG and LRYGB regarding early complications and mortality 3.6% versus 5.8% (p = 0.15) and 0.1% versus 0.8% (p = 0.27). Patients who underwent LRYGB had more late complications compared with those who underwent LSG (0.07% and 0.03%, p = 0.001). There was no difference in terms of weight loss at the end of 1 year. Patients who underwent LRYGB had a better resolution of obesity-related comorbidities, not statistically significant. CONCLUSION: LRYGB has better efficacy when compared with LSG. However, high-risk elderly patients should be considered for LSG given the lesser morbidity and comparable efficacy with LRYGB.

Assessment of Mass Effect Sign at High-Resolution Computed Tomography in Prediction of Cholesteatoma.

OBJECTIVE: The aim of this study was to assess the accuracy of mass effect sign in the diagnosis of cholesteatoma at high-resolution computed tomography (HRCT). METHODS: This prospective study included 32 ears in 24 patients with chronic otitis media who underwent HRCT of the temporal bone. Otoscopic and operative notes were recorded. Image analysis was done both qualitatively and quantitatively. In the qualitative analysis, mass effect was evaluated visually by comparing both ears together in 4 certain anatomical sites. Ossicular erosions, erosion of tegmen tympani, erosion of tympanic segment of facial nerve canal, and the presence of lobulated nondependent opacity were also evaluated. In the quantitative analysis, we calculated the difference between the distances of the described anatomical sites in both ears. RESULTS: Qualitative analysis of mass effect sign showed 97.1% accuracy in detecting cholesteatoma. Ossicular erosions showed 69.2% accuracy in the diagnosis of cholesteatoma. In the quantitative analysis, we found that the cutoff point of 0.45 mm in the difference of aditus measure between both ears showed 85.3% accuracy in differentiating cholesteatoma from otitis media. The cutoff point of 0.75 mm in the differences in supratubal measure showed 86.1% accuracy. The cutoff point of 0.45 mm in the medial to incus measure showed 100% accuracy. CONCLUSION: High-resolution computed tomography is highly valuable for the detection of mass effect sign, which has great importance in diagnosing cholesteatoma.

The misplaced cochlear implant electrode array.

OBJECTIVES/HYPOTHESIS: Evaluation of the clinical, electrophysiologic findings, the management plans of the misplaced cochlear implant electrode array and the possible causes of misplacement. Also to provide recommendations to prevent a repeat of cochlear implant electrode misplacement into abnormal sites. STUDY DESIGN: Retrospective study. METHODS: Pediatric cochlear implant recipients implanted from January 2012 till January 2018 whose electrode arrays were misplaced outside the cochlea into the surrounding structures. RESULTS: Eight pediatric cochlear implant recipients, were identified to have a misplaced cochlear implant electrode array. Different sites of improper placement included one case in the eustachian tube, another one in the vestibule, one electrode array was found to be in the petrous apex lateral to the internal carotid canal, and another one in the internal auditory canal (IAC), and in three cases the electrode arrays were packed in the hypotympanum, and lastly an electrode array recoiled after perfect insertion and was found to be in the facial recess. Six cases were initially identified immediate because of their poor intraoperative implant testing which prompted imaging while in two cases, the one found in the petrous apex and the other one in the internal auditory canal (IAC) were diagnosed several months after surgery due to unsatisfactory auditory skills development or absent behavioral responses following implantation. CONCLUSIONS: Electrode array misplacement may be due to either failure to identify the anatomical landmarks during surgery specially the infracochlear air cell track or unidentified inner ear malformation. The routine use of intraoperative electrophysiologic testing and postoperative imaging should help to avoid such complications. Misplacement is a rare but still correctable complication after cochlear implant surgery. The diagnosis of misplacement can be delayed for years and in this occasion, it is suspected when benefit from the implant is limited or absent. Once misplacement is diagnosed revision surgery has to be done.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives.

The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

Hydrophobized triphenyl phosphonium derivatives for the preparation of mitochondriotropic liposomes: choice of hydrophobic anchor influences cytotoxicity but not mitochondriotropic effect.

CONTEXT: Nanocarrier-based strategies to achieve delivery of bioactives specifically to the mitochondria are being increasingly explored due to the importance of mitochondria in critical cellular processes. OBJECTIVE: To test the ability of liposomes modified with newly synthesized triphenylphosphonium (TPP)-phospholipid conjugates and to test their use in overcoming the cytotoxicity of stearyl triphenylphosphonium (STPP)-modified liposomes when used for delivery of therapeutic molecules to the mitochondria. METHODS: TPP-phospholipid conjugates with the dioleoyl, dimyristoyl or dipalmitoyl lipid moieties were synthesized and liposomes were prepared with these conjugates in a 1 mol% ratio. The subcellular distribution of the liposomes was tested by confocal microscopy. Furthermore, the liposomes were tested for their effect on cell viability using a MTS assay, on cell membrane integrity using a lactate dehydrogenase assay and on mitochondrial membrane integrity using a modified JC-1 assay. RESULTS: The liposomes modified with the new TPP-phospholipid conjugates exhibited similar mitochondriotropism as STPP-liposomes but they were more biocompatible as compared to the STPP liposomes. While the STPP-liposomes had a destabilizing effect on cell and mitochondrial membranes, the liposomes modified with the TPP-phospholipid conjugates did not demonstrate any such effect on biomembranes. CONCLUSIONS: Using phospholipid anchors in the synthesis of TPP-lipid conjugates can provide liposomes that exhibit the same mitochondrial targeting ability as STPP but with much higher biocompatibility.

Synthesis of triphenylphosphonium phospholipid conjugates for the preparation of mitochondriotropic liposomes.

Surface modification of liposomes with a ligand is facilitated by the conjugation of the ligand to a hydrophobic molecule that serves to anchor the ligand to the liposomal bilayer. We describe here a simple protocol to conjugate a triphenylphosphonium group to several commercially available functionalized phospholipids. The resulting triphenylphosphonium conjugated lipids can be used to prepare liposomes that preferentially associate with mitochondria when exposed to live mammalian cells in culture.

Comparison of different computed tomography post-processing modalities in assessment of various middle ear disorders.

Several anatomic structures of the middle ear are not optimally depicted in the standard axial and coronal planes. Several 2D and 3D image-processing modalities are currently available for CT examinations in clinical radiology departments. Till now 3D reconstructions of the temporal bone have not been widely used yet, and attracted only academic interest. The aim of this study was to compare axial (source images), 2D and 3DCT post-processing modalities, and to evaluate the value of 3D reconstructed images/virtual endoscopy (VE) in assessment of various middle ear disorders for identification of the best modality/view for assessment of a particular middle ear structure or pathology. 40 patients with various middle ear disorders, planned for surgical intervention were included in prospective study. Multi-slice CT was performed for all patients. Scans were acquired in the axial plane. The axial source datasets were utilized for generation of 2D reformations and 3D reconstructed images. All studied images were divided into three categories: axial (source images), 2D reformations (MPR and sliding-thin-slab MIP) and 3D reconstruction (virtual endoscopy). The visibility of middle ear structures and pathologies with each modality were scored qualitatively using three-point scoring system in reference to operative findings. Stapes superstructure and footplate, incudostapedial joint, oval and round windows, tympanic segment of the facial nerve and tegmen were not optimally depicted in the axial plane. Sinus tympani and facial recess were best visualized with axial images or VE. 3D reconstruction/VE allowed good visualization of all parts of ossicular chain except stapes superstructure. Regarding pathologic changes, 2D reformations and 3D reconstructed images allowed better visualization of erosion of ossicles and tegmen. 3D reconstruction/VE did not allow detection of foci of otospongiosis. 2D reformations can be considered the mainstay in assessment of most middle ear structures and pathologies. 3D reconstruction/VE seems to provide a useful method for a preoperative general overview of the middle ear anatomy, particularly for the ossicular chain, round window and retrotympanum.

Antidiabetic agents: past, present and future.

Treatment of diabetes mellitus requires, at a certain stage of its course, drug intervention. This article reviews the properties of available antidiabetic medications and highlights potential targets for developing newer and safer drugs. Antidiabetic agents are grouped in the article as parts I, II and III according to the history of development. Part I groups early developed drugs, during the 20th century, including insulin, sulfonylureas, the metiglinides, insulin sensitizers, biguanides and α-glucosidase inhibitors. Part II groups newer drugs developed during the early part of the 21st century, the past decade, including GLP-1 analogs, DPP-VI inhibitors, amylin analogs and SGLT2 inhibitors. Part III groups potential targets for future design of newer antidiabetic agents with less adverse effects than the currently available antidiabetic drugs.

Cyanoacrylate: a handy tissue glue in maxillofacial surgery: our experience in alexandria, egypt.

Cyanoacrylate tissue glue has been widely used in different surgical applications. It is easy to apply and can save considerable time and effort. Reports including series of oral and maxillofacial cases are yet to be well documented. We report our experience using cyanoacrylate tissue glue in the head and neck region in 165 patients. We have used it for indications including orbital floor graft fixation, cleft lip and palate repair, oral dressing, skin graft fixation, nasal splinting, immobilisation of traumatised teeth, management of chyle leak during neck dissection and wound closure. We have not had any complications from using cyanoacrylate. It is found to be safe and effective in different indications it is used for without undue hazards. The role of cyanoacrylate in oral and maxillofacial surgery needs further research.

Design, synthesis and biological evaluation of a series of thioamides as non-nucleoside reverse transcriptase inhibitors.

A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8-thioamides exhibited enzyme inhibitory activities with IC(50) values below 100 microM. While compound (2) exhibited activity against the mutant strain L100I with IC(50) of 70.1 microM, compound (4) showed activity against the mutant strain K103N with IC(50) of 92.7 microM, and compound (8) with activity against the wild type enzyme with IC(50) of 8.9 microM. Each of the three thioamides could serve as a lead compound for further activity optimization.

Instructional model to teach clinically relevant medicinal chemistry.

The relevance of medicinal chemistry to pharmacy practice has been questioned by many pharmacy educators as more emphasis has been placed on linking clinical knowledge and practice to pharmacy student educational outcomes. Faculty teaching in medicinal chemistry and other biomedical and pharmaceutical science courses have embraced this challenge. Various teaching methods and approaches within medicinal chemistry that emphasize application of this knowledge have been sought to improve the usefulness of this scientific discipline to the future careers of students. The newly revised ACPE guidelines and standards have reemphasized the role of the sciences in the curriculum. With this mandate, it is essential that all science faculty members adjust the way they teach to meet the new desired outcomes for pharmacy graduates. This manuscript describes an instructional model for teaching medicinal chemistry explicitly designed to meet these outcomes. A process of collaboration between experienced pharmacy faculty scholars was used to derive this approach. Pedagogy for cognitive and affective learning was incorporated. A case study using a representative drug class is presented to illustrate this model.

Design, synthesis, and biological testing of thiosalicylamides as a novel class of calcium channel blockers.

The current research aimed to investigate the importance of the heterocyclic ring system in the structure of the cardiovascular drug diltiazem for its calcium channel blocking activity. The manuscript describes the design, synthesis, and biological testing of a total of 10 S-(p-methoxybenzyl), N-substituted thiosalicylamides as a series of non-cyclic compounds derived from diltiazem's structure. The new compounds maintained all diltiazem pharmacophores except the thiazepine ring system. In vitro evaluation of the new series for calcium channel blocking effects revealed moderate activities with IC50 values in the range of 4.8-56.0 microM. The data suggest that the ring system is not essential for activity; however, its absence leads to a considerable drop of activity relative to that of diltiazem (IC50=0.3 microM). Compounds of the current series showed optimum activity when the aliphatic alkyl chain on the salicylamide nitrogen is part of a piperidine or piperazine ring system substituted at the terminal nitrogen with a benzyl group.