Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis

Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this. Here we report on the membrane permeabilizing features of GSDME by monitoring the influx and efflux of dextrans of different sizes into/from anti-Fas-treated L929sAhFas cells undergoing apoptosis-driven secondary necrosis. We found that GSDME accelerates cell lysis measured by SYTOX Blue staining but does not affect the exposure of phosphatidylserine on the plasma membrane. Furthermore, loss of GSDME expression clearly hampered the influx of fluorescently labeled dextrans while the efflux happened independently of the presence or absence of GSDME expression. Importantly, both in- and efflux of dextrans were dependent on their molecular weight. Altogether, our results demonstrate that GSDME regulates the passage of compounds together with other plasma membrane destabilizing subroutines.

ENDOSCOPIC CARTILAGE TYMPANOPLASTY. OUR TECHNIQUE AND EXPERIENCE OF 157 CASES

Objective: To assess the graft take rate and hearing gain in trans-canal endoscopic tympanoplasty Study Design: Descriptive study. Place and Duration of Study: Pakistan Naval Ship Hafeez, Islamabad Pakistan, form Dec 2015 to Jun 2018 Methodology: All patients with dry central perforations of >3 months history were included in the study. All Patients with perforations of pars tensa were booked for endoscopic cartilage tympanoplasty. All perforations were divided into four types small, medium, large and subtotal or total based on size of the tympanic membrane perforations. Small perforations involving <25% area of Pars Tensa. Medium perforation are Perforations involving 25-50% of Tympanic membrane. Large perforations include Perforations involving 50-75% of pars tensa. Subtotal or total perforations are defined as perforations with >75% perforation of the tympanic membranes. Wet Ears and perforations involving the Pars Flacida were excluded from the study. Preoperative Audiogram was carried out for all patients and A-B Gap were noted for all groups separately so as the demographic data including age and gender. Success was defined as complete closure of Tympanic membrane perforation at 3 months. All patients were operated with 0 Degree 3mm, 14cm rigid endoscope under general anesthesia. Results: Mean age of patients was. 37 years and standard deviation was 12.34 (range 12-58 years). Out of total 157 cases 81 patients male were males (51%) and 76 patients were females (49). Out of 157 ears operated 146 Perforations healed completely an overall success rate of 92%. Patients with small perforations had 100 percent success.....

To Compare the Graft Uptake in Permeatal versus Postaural Approaches in Myringoplasty

Objective: To compare the graft uptake in permeatal versus postaural approaches in myringoplasty. Study design: Cross sectional comparative Place and Duration of Study: Department of ENT, Head and Neck Surgery, Pakistan Institute of Medical Sciences/Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan from 1st March 2018 to 31st December 2018. Methodology: Seventy two patients were classified into two equal groups. Thirty six patients underwent myringoplasty by permeatal approach and thirty six patients underwent postaural approach. Those patients were included who had mucosal type moderate central perforation with inactive disease with age 15-42 years and those patients were excluded who had small, subtotal, total, squamosal type atticoantral tympanic membrane perforation, with comorbidities and pregnancy. Results: Thirty seven were (51.4 %) males and 35 (48.6%) were females. In both the groups the success of graft uptake was 52 (72.2%) patients and graft rejection in 20 (27.8%) patients. In each group there were 36 patients. The graft uptake in permeatal approach was 30 patients (83.3%), while the graft uptake in postaural approach was 22 (61.1%) patients. The overall graft uptake in permeatal approach is more as compared to postaural approach (p=0.035). Conclusion: The permeatal approach is better than the postaural approach in terms of graft uptake in medium sized central perforations in myringoplasty. Key words: Myringoplasty, Tympanoplasty, Permeatal, Postauricular

Displacement of the full body of a dental implant into the sinus space without membrane perforation and subsequent osseointegration: a case report

An increasing number of studies have investigated the use of osteotome sinus floor elevation (OSFE) with simultaneous implant placement for maxillary sinus floor residual bone height (RBH) <4 mm. Many studies have reported good clinical results, but very few have reported complications related to this procedure. Here, the case of a 50-year-old female patient with an RBH in the left upper posterior region of 1–4 mm, who underwent OSFE with simultaneous placement of three Bicon short® implants, is described. One of the implants was found to be displaced during the second-stage surgery. The displaced implant was removed using piezosurgery, OSFE with simultaneous implant placement was repeated, and the missing tooth was reconstructed 6 months later. This case suggests that OSFE with simultaneous implant placement is feasible for severely atrophic maxillary sinus floor, but carries a risk of implant displacement.

Deep anterior lamellar and penetrating keratoplasty in developed and advanced stages of keratoconus

This article presents the results of surgical treatment of 30 patients (30 eyes) with keratoconus stage 3-4, which were divided into two groups depending on the performed surgery technique. Deep anterior lamellar keratoplasty (DALK) was performed on 20 eyes using a femtosecond laser and the surgery technique including separation of the residual corneal stroma using the "big bubble" technique, and in some cases using the manual dissection technique. In 25% of cases (5 out of 20 eyes), the DALK operation was complicated by Descemet's membrane perforation and therefore, the surgical intervention was completed by switching to penetrating keratoplasty (PK). These patients were excluded from the DALK group and included in the PK group, who underwent penetrating keratoplasty (15 eyes). The maximum follow-up period was 2 years. After DALK transparent engraftment was achieved in all cases, and after PK in 93.4% of cases, in one case (6.6%) graft rejection was observed. Key words: keratoconus, surgical treatment, deep anterior lamellar keratoplasty, penetrating keratoplasty.

A clinical study of traumatic tympanic membrane perforation

<p><strong>Background:</strong> Tympanic membrane (TM) which forms the partition between external auditory canal and middle ear may be ruptured by trauma. Traumatic TM perforation is a commonly observed condition. Though, several therapeutic interventions have been described, conservative follow-up until spontaneous complete recovery is the most common choice.</p><p><strong>Methods:</strong> It was a prospective cohort study conducted during a period of 10 months from July 2020 to April 2021, carried out in 30 patients who presented to outpatient department of ENT and casualty of Hassan institute of medical sciences hospital with traumatic TM perforation. After taking informed consent, detailed history was taken, thorough examination of ear was performed and characteristics of perforation were noted. Pure tone audiometry (PTA) was conducted, data was statistically analysed.</p><p><strong>Results:</strong> Mean age group was 33.1 years and 73.3% were males. Ear pain was the commonest symptom with accidental trauma being the most common cause. 70% of them had left TM perforation and posteroinferior quadrant was mostly involved.</p><p><strong>Conclusions:</strong> Traumatic TM perforation is commonly seen in young adults following accidental trauma and assault. Earache, sudden hearing loss and tinnitus are the common symptoms. Most of the cases heal spontaneously with conservative management.</p>