The accuracy of asynchronous tele-screening for detecting dental caries in patient-captured mobile photos: A pilot study.

Objectives: Unaided visual inspection is a primary dental screening technique. Given the uneven distribution of dental services and prolonged waiting periods, an alternative screening approach is required to increase access to dental care. The purpose of this study was to evaluate the accuracy and reliability of tele-screening for detecting dental caries using mobile intra-oral photos taken by participants. Methods: Dental care seekers attending Umm Al-Qura University Teaching Dental Hospital in 2022 were invited to participate in this study. The participants were initially examined by dental interns at the hospital under the supervision of faculty dentists (reference standard) before intra-oral photos were acquired by a trained sixth-year dental student using a Samsung S10 camera. Following an introduction to the photography guide, the same participants then took intra-oral photos of their teeth at home using their mobile devices, which were all uploaded to WhatsApp for later review. Two trained dental reviewers (sixth-year dental students) independently reviewed the intra-oral photos. Sensitivity, specificity, and Kappa scores were estimated to assess the performance of the tele-screening approach relative to the reference unaided dental examination. Results: Twenty-three participants, with a mean age of 30 ± 12 years, were enrolled. The mean decayed, missing, and filled teeth (DMFT) was 13.43 ± 5.48. Patient-delivered tele-screening demonstrated a sensitivity, specificity, and inter-rater reliability kappa of 94 %, 90 %, and 0.81, respectively, when compared to unaided dental examination. Dentist-delivered tele-screening approach demonstrated a sensitivity of 88-89 %, specificity of 88-91 %, and kappa score of 0.75-0.79 relative to unaided dental examination. Conclusions: This study demonstrated that the tele-screening approach based on reviewing intra-oral photos taken by participants can be a valid and reliable alternative to unaided dental examination. This is important for ensuring sustainable access to dental care.

A redox state-dictated signalling pathway deciphers the malignant cell specificity of CD40-mediated apoptosis.

CD40, a member of the tumour necrosis factor receptor (TNFR) superfamily, has the capacity to cause extensive apoptosis in carcinoma cells, while sparing normal epithelial cells. Yet, apoptosis is only achieved by membrane-presented CD40 ligand (mCD40L), as soluble receptor agonists are but weakly pro-apoptotic. Here, for the first time we have identified the precise signalling cascade underpinning mCD40L-mediated death as involving sequential TRAF3 stabilisation, ASK1 phosphorylation, MKK4 (but not MKK7) activation and JNK/AP-1 induction, leading to a Bak- and Bax-dependent mitochondrial apoptosis pathway. TRAF3 is central in the activation of the NADPH oxidase (Nox)-2 component p40phox and the elevation of reactive oxygen species (ROS) is essential in apoptosis. Strikingly, CD40 activation resulted in down-regulation of Thioredoxin (Trx)-1 to permit ASK1 activation and apoptosis. Although soluble receptor agonist alone could not induce death, combinatorial treatment incorporating soluble CD40 agonist and pharmacological inhibition of Trx-1 was functionally equivalent to the signal triggered by mCD40L. Finally, we demonstrate using normal, 'para-malignant' and tumour-derived cells that progression to malignant transformation is associated with increase in oxidative stress in epithelial cells, which coincides with increased susceptibility to CD40 killing, while in normal cells CD40 signalling is cytoprotective. Our studies have revealed the molecular nature of the tumour specificity of CD40 signalling and explained the differences in pro-apoptotic potential between soluble and membrane-bound CD40 agonists. Equally importantly, by exploiting a unique epithelial culture system that allowed us to monitor alterations in the redox-state of epithelial cells at different stages of malignant transformation, our study reveals how pro-apoptotic signals can elevate ROS past a previously hypothesised 'lethal pro-apoptotic threshold' to induce death; an observation that is both of fundamental importance and carries implications for cancer therapy.

Therapeutic rather than prophylactic platelet transfusion policy for severe thrombocytopenia during liver transplantation.

Platelet transfusion (PTx) has been identified as an important risk factor for morbidity and mortality after liver transplantation (LTx). Our aim was to evaluate the safety of therapeutic rather than prophylactic PTx policy in severe thrombocytopenic patients undergoing LTx. Recipients of LTx were divided into two groups: group I (GI) (n = 76) platelet count (PC) ≥ 50 × 10(9)/l and group II (GII) PC < 50 × 109/l (n = 76). Platelets were transfused following a thromboelastometry protocol and clinical signs of diffuse bleeding. Both groups were compared regarding hemoglobin (Hb), international normalized ratio (INR), fibrinogen level, blood loss (BL), blood products required, percentage of bloodless surgery, duration of mechanical ventilation, ICU stay, and vascular complications. Each group was further subdivided according to PTx into (GI NPTx and GII NPTx) with no platelet transfusion (NPTx) and (GI PTx and GII PTx) received PTx. These subgroups were further compared for some variables. Base line Hb was significantly higher while INR was significantly lower in GI.75% avoided PTx in GII. Comparisons of BL, packed red blood cells (PRBCs), and cryoprecipitate transfusion were insignificant. Fresh frozen plasma (FFP) transfusion was higher and the percentage of bloodless surgery was lower in GII. In GII, PC increased after start of surgery. Two cases of hepatic artery thrombosis in GI and one in GII were recorded. Recovery of platelets was quicker, and duration of mechanical ventilation and ICU stay was shorter in NPTx patients regardless the base line PC. Cut-off values of PC 30 × 10(9)/l (with sensitivity 73.7% and specificity 78.8%, p < 0.01), BL of 3750 ml in GI (sensitivity of 75% and specificity of 69%, p < 0.01) and of 3250 ml in GII (sensitivity of 84.2% and specificity of 87.7% (p < 0.01)) could indicate the need of PTx. With therapeutic approach, 75% of patients in GII could avoid unnecessary PTx with its hazards without excessive bleeding. PC in GII increased intraoperatively, PTx may lead to delayed recovery of platelets, increased duration of mechanical ventilation and ICU stay. The given cut-off values may help to guide PTx.