Fracture resistance and failure mode of three esthetic CAD-CAM post and core restorations.

BACKGROUND: The rising demand for improved aesthetics has driven the utilization of recently introduced aesthetic materials for creating custom post and core restorations. However, information regarding the fracture resistance of these materials remains unclear, which limits their practical use as custom post and core restorations in clinical applications. AIM OF THE STUDY: This study aimed to evaluate the fracture resistance of three non-metallic esthetic post and core restorations and their modes of failure. MATERIALS AND METHODS: Thirty-nine single-rooted human maxillary central incisors were endodontically treated. A standardized post space preparation of 9mm length was performed to all teeth to receive custom-made post and core restorations. The prepared teeth were randomly allocated to receive a post and core restoration made of one of the following materials (n=13): glass fiber-reinforced composite (FRC), polyetheretherketone (PEEK) and polymer-infiltrated ceramic-network (PICN). An intraoral scanner was used to scan all teeth including the post spaces. Computer-aided design and computer-aided manufacturing (CAD-CAM) was used to fabricate post and core restorations. Post and core restorations were cemented using self-adhesive resin cement. All specimens were subjected to fracture resistance testing using a universal testing machine. Failure mode analysis was assessed using a stereomicroscope and SEM. The data was statistically analyzed using One-Way ANOVA test followed by multiple pairwise comparisons using Bonferroni adjusted significance level. RESULTS: Custom PEEK post and core restorations displayed the least fracture load values at 286.16 ± 67.09 N. In contrast, FRC exhibited the highest average fracture load at 452.60 ± 105.90 N, closely followed by PICN at 426.76 ± 77.99 N. In terms of failure modes, 46.2% of specimens with PICN were deemed non-restorable, while for PEEK and FRC, these percentages were 58.8% and 61.5%, respectively. CONCLUSIONS: Within the limitation of this study, both FRC and PICN demonstrated good performance regarding fracture resistance, surpassing that of PEEK.

Fine-mapping of a major locus for Fusarium wilt resistance in flax (Linum usitatissimum L.).

KEY MESSAGE: Fine-mapping of a locus on chromosome 1 of flax identified an S-lectin receptor-like kinase (SRLK) as the most likely candidate for a major Fusarium wilt resistance gene. Fusarium wilt, caused by the soil-borne fungal pathogen Fusarium oxysporum f. sp. lini, is a devastating disease in flax. Genetic resistance can counteract this disease and limit its spread. To map major genes for Fusarium wilt resistance, a recombinant inbred line population of more than 700 individuals derived from a cross between resistant cultivar 'Bison' and susceptible cultivar 'Novelty' was phenotyped in Fusarium wilt nurseries at two sites for two and three years, respectively. The population was genotyped with 4487 single nucleotide polymorphism (SNP) markers. Twenty-four QTLs were identified with IciMapping, 18 quantitative trait nucleotides with 3VmrMLM and 108 linkage disequilibrium blocks with RTM-GWAS. All models identified a major QTL on chromosome 1 that explained 20-48% of the genetic variance for Fusarium wilt resistance. The locus was estimated to span ~ 867 Kb but included a ~ 400 Kb unresolved region. Whole-genome sequencing of 'CDC Bethune', 'Bison' and 'Novelty' produced ~ 450 Kb continuous sequences of the locus. Annotation revealed 110 genes, of which six were considered candidate genes. Fine-mapping with 12 SNPs and 15 Kompetitive allele-specific PCR (KASP) markers narrowed down the interval to ~ 69 Kb, which comprised the candidate genes Lus10025882 and Lus10025891. The latter, a G-type S-lectin receptor-like kinase (SRLK) is the most likely resistance gene because it is the only polymorphic one. In addition, Fusarium wilt resistance genes previously isolated in tomato and Arabidopsis belonged to the SRLK class. The robust KASP markers can be used in marker-assisted breeding to select for this major Fusarium wilt resistance locus.

The long non-coding RNA ZFAS1 promotes colorectal cancer progression via miR200b/ZEB1 axis.

BACKGROUND: Colorectal cancer (CRC) is a common tumor worldwide. CRC is influenced by several types of miRNAs and long non-coding RNAs. This study aims to evaluate the correlation of lncRNA ZFAS1/ miR200b/ ZEB1 protein with presence of CRC. METHODS: Quantitative real-time polymerase chain reaction was used to measure serum expression of lncRNA ZFAS1 and microRNA-200b in 60 CRC patients and 28 control subjects. ZEB1 protein in serum was measured by ELISA. RESULTS: Lnc ZFAS1 and ZEB1 were up-regulated in CRC patients in compare to control subjects while miR-200b was down-regulated. There was a linear correlation between ZAFS1 expression and miR-200b and ZEB1 in CRC. CONCLUSION: ZFAS1 is a key player of CRC progression and could be a potential therapeutic target by sponging miR-200b. In-addition the association between ZFAS1, miR-200b and ZEB1 highlights their potential value as a novel diagnostic biomarker in human CRC.

Supplementing sodium butyrate to limit-fed heifers: Effects on growth, coccidiosis, urinary purine derivatives, and apparent total-tract nutrient digestibility.

The objective of this study was to assess the growth, apparent total-tract digestibility of nutrients, the prevalence of coccidia, and purine derivatives in postweaning heifers when limit-fed a diet supplemented with sodium butyrate (SB). A 12 wk randomized complete block experiment was conducted using 24 Holstein heifers (92.8 d ± 1.9 d of age and initial body weight [BW] of 99.6 ± 15.2 kg [mean ± standard deviation]). Treatments were 100 g soybean meal (control; CON) and 0.75 g of SB/kg of BW + 100 g soybean meal (SB). Diets were formulated to contain 16.4% crude protein, 2.27 Mcal/kg metabolizable energy (ME), and fed at a feed out rate of 2.15% of BW on a dry matter basis. Intakes were recorded daily while growth measurements and BW were recorded weekly. Urine and fecal samples were taken every 2 wk. On d 42 through d 49 an apparent total-tract digestibility phase took place using acid detergent insoluble ash as a marker. Growth measurements were similar among treatments except CON heifers grew longer and tended to be taller at the withers. A trend was observed for CON animals to have lower levels of coccidian oocytes by week. Heifers fed SB had lower blood glucose levels and higher levels of ketones in their blood. Urinary volume was greater for heifers fed SB throughout the 12 wk study. Total purine derivatives were greater in CON heifers. Dry matter, organic matter and acid detergent fiber digestibilities were greater for heifers fed SB compared with CON heifers. Crude protein, neutral detergent fiber, and ash digestibilities tended to be greater in heifers fed SB than in CON heifers. These results suggested no growth benefit of supplementing SB to limit-fed heifers; however, apparent total-tract fiber, ash, and crude protein digestibilities were improved in the SB fed heifers likely due to improved ruminal and intestinal development.

Kasr Alainy simplified uterine preserving surgery for conservative management of placenta accreta spectrum (PAS): A modified surgical approach.

OBJECTIVE: The incidence of placenta accreta spectrum (PAS) is rising rapidly due to the global surge in Caesarean delivery. It is associated with significant maternal morbidity and mortality. It is usually managed with Caesarean hysterectomy. However, uterine preserving surgeries can have advantages over Caesarean hysterectomy and intentional placental retention techniques. STUDY DESIGN: We present a modified technique of uterine preserving surgery that uses a safe approach for placental bed surgical devascularization. This is followed by resection of the invaded uterine segment and uterine wall reconstruction. RESULTS: The technique was used in the management of 20 patients with antenatally suspected PAS that were confirmed at laparotomy. It was successful in preserving the uterus in 18/20 (90 %) women. The mean intraoperative blood loss in was 1305 CC (SD: +361.6) with a mean operative time of 123 min (SD: ±38.7). There was only one urinary bladder injury and no other maternal morbidity. CONCLUSION: Our surgical technique is safe and may be useful for conservative surgical management of PAS, particularly in low- and middle-income countries, where access to complex resources, such as interventional radiology, is limited.

Filociclovir is a potent inhibitor of human adenovirus F41.

Clusters of acute non HepA-E hepatitis cases in previously healthy children have been reported globally. At least, 1010 cases were identified in 35 countries, 5% of those cases required liver transplantation and 2% died. The exact cause is not yet known, but there is circumstantial evidence suggesting that human adenovirus F41 (HAdV-F41) might be playing a role. No antiviral drug has been approved for treating human adenovirus infections. Furthermore, HAdV-F41 is notoriously difficult to grow in cell culture, which hindered studying the efficacy of an antiviral compound against this virus. Here, we show that filociclovir (FCV), a nucleoside analog, is a potent inhibitor of HAdV-F41 in cell culture using 2 approaches, namely immunostaining of infected cells and virus yield reduction assay. The activity of FCV was compared to 3 other known antivirals: cidofovir (CDV), ganciclovir (GCV) and valganciclovir (VGCV). Among the 4 compounds examined in this study, FCV was the most potent, with an EC50 of 3.5 µM. These compounds can be ranked by potency as follows: FCV > CDV > GCV ≥ VGCV. In addition, FCV was 10-fold more potent than CDV in a virus yield reduction assay. This report provides timely and valuable methodologies to the research community for testing antivirals against HAdV-F41. Our findings also support the continued development of FCV for various therapeutic applications, including pediatric hepatitis, if a causal relationship is firmly established in the future.

The economic burden of TB faced by patients and affected families in Papua New Guinea.

BACKGROUND The costs associated with TB disease can be catastrophic for patients, affecting health and socioeconomic outcomes. Papua New Guinea (PNG) is a high TB burden country and the costs associated with TB are unknown.METHODS We undertook a national survey of TB patients to determine the magnitude of costs associated with TB in PNG, the proportion of households with catastrophic costs and cost drivers. We used a cluster sampling approach and recruited TB patients from health facilities. Descriptive statistics were used to analyse the costs and cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs.RESULTS We interviewed 1,000 TB patients; 19 (1.9%) of them had multidrug-resistant TB (MDR-TB). Costs due to TB were attributable to income loss (64.4%), non-medical (29.9%) and medical (5.7%) expenses. Catastrophic costs were experienced by 33.9% (95% CI 31.0-36.9) of households and were associated with MDR-TB (aOR 4.47, 95% CI 1.21-16.50), hospitalization (aOR 3.94, 95% CI 2.69-5.77), being in the poorest (aOR 3.52, 95% CI 2.43-5.10) or middle wealth tertiles (aOR 1.51, 95% CI 1.03-2.21) or being employed (aOR 2.02, 95% CI 1.43-2.89).CONCLUSION The costs due to TB disease were catastrophic for one third of TB-affected households in PNG. Current support measures could be continued, while new cost mitigation interventions may be considered where needed.

Glycemic Status among Pregnant Women during 24th to 28th Gestational Age.

Gestational diabetes mellitus (GDM) is a heterogeneous group of metabolic disorder, which result in varying degrees of maternal hyperglycemia and pregnancy associated risk. Glucose intolerance usually returns to normal range within 6 weeks after delivery. This study was undertaken to determine the glycemic status who attended for antenatal care. This study enrolled pregnant women, with their gestational age between 24th - 28th weeks. This analytical cross sectional study was carried out in the department of Biochemistry, BIRDEM General Hospital, Dhaka, Bangladesh from July 2014 to June 2015. Total 135 subjects were selected to evaluate the glycemic status among Bangladeshi pregnant women attending BIRDEM General Hospital. Among them 41 were GDM subjects and 94 were non GDM subjects. The mean fasting plasma glucose values (mmol/L) and 2 hours after 75gm glucose values of GDM were 6.06±1.26 and 9.78±2.74 respectively compared to non GDM patients were 4.82±0.38 and 7.26±0.41 respectively and the mean of HbA1C (%) of GDM and non GDM were 5.87±0.73 and 5.43±0.31 respectively.

Silent Sinus Syndrome: A Case Report.

To describe a case of silent sinus syndrome in the perspective of imaging studies, on 2 January 2020 we present this case of a 26-year-old Bangladeshi man with unilateral right facial asymmetry and no sino-nasal symptoms. He was referred to the Ophthalmology Department with complain of right palpebral ptosis and facial asymmetry for 7 months. On physical examination, painless enophthalmos and hypo globus of the right eye was seen. The computed tomography scan of the paranasal air sinuses showed opacification of the right maxillary sinus along with retraction of the walls of the sinus. Regardless of the clinical doubt, the conclusion can only be given by imaging studies, radiologist play a key role here.

From bad to worse: airline boarding changes in response to COVID-19.

Airlines have introduced a back-to-front boarding process in response to the COVID-19 pandemic. It is motivated by the desire to reduce passengers' likelihood of passing close to seated passengers when they take their seats. However, our prior work on the risk of Ebola spread in aeroplanes suggested that the driving force for increased exposure to infection transmission risk is the clustering of passengers while waiting for others to stow their luggage and take their seats. In this work, we examine whether the new boarding processes lead to increased or decreased risk of infection spread. We also study the reasons behind the risk differences associated with different boarding processes. We accomplish this by simulating the new boarding processes using pedestrian dynamics and compare them against alternatives. Our results show that back-to-front boarding roughly doubles the infection exposure compared with random boarding. It also increases exposure by around 50% compared to a typical boarding process prior to the outbreak of COVID-19. While keeping middle seats empty yields a substantial reduction in exposure, our results show that the different boarding processes have similar relative strengths in this case as with middle seats occupied. We show that the increased exposure arises from the proximity between passengers moving in the aisle and while seated. Such exposure can be reduced significantly by prohibiting the use of overhead bins to stow luggage. Our results suggest that the new boarding procedures increase the risk of exposure to COVID-19 compared with prior ones and are substantially worse than a random boarding process.

Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model.

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC50) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC50 for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.

Bone-anchored maxillary protraction in patients with unilateral cleft lip and palate.

OBJECTIVES: To assess the effectiveness of bone-anchored maxillary protraction (BAMP) in patients with unilateral cleft lip and palate (UCLP) and whether it was enhanced when preceded by maxillary expansion. MATERIALS AND METHODS: The sample consisted of 28 growing children (9-13 years old) with UCLP and Class III malocclusion. They were divided into two equal groups. In group I, patients were treated with BAMP not preceded by maxillary expansion. In group II, patients were treated with BAMP preceded by maxillary expansion. To assess treatment changes in three dimensions, Cone-beam computed tomography images were taken 1 week after surgical placement of the miniplates (T1) and after 9 months of treatment (T2). RESULTS: BAMP produced forward movement of the maxilla in both groups (3.17 mm) and (3.37 mm) respectively, without significant differences between the two groups except for clockwise rotation of the palatal plane in group I (1.60). CONCLUSIONS: BAMP is an effective treatment modality for correcting midface deficiency in patients with UCLP whether or not maxillary expansion was carried out.

Systematic Review on Apolipoprotein E: A Strong Genetic Cause of Hemorrhagic Stroke.

Stroke is one of the commonest causes of mortality among the world. Hemorrhagic stroke accounts nearly 15% of all the strokes. Different risk factors have been identified, of them hypertension, anti-coagulation therapy and previous history of ischemic strokes are significant. Regarding the genetic causes of intracerebral hemorrhage (ICH) monogenic causes play a small role. It was found that Apolipoprotein E (APOE) gene has a strong association with ICH. This is a 299 amino acids long protein located in chromosome 19. APOE has three alleles, they are epsilon 2, 3 and 4. Total 10 meta-analysis were reviewed in this article which involved 52,705 participants. When looking for the association, ∈2 and ∈4 showed positive and ∈3 showed negative association with ICH. Association of ∈4 (OR mean 1.77) was stronger than that of ∈2 (OR mean 1.71).

Cardiovascular disease risk factors among school children of Bangladesh: a cross-sectional study.

OBJECTIVE: Primarily, we assessed the distribution of cardiovascular disease (CVD) risk factors among school children living in urban and rural areas of Bangladesh. In addition to this, we sought the association between place of residence and modifiable CVD risk factors among them. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study was conducted among 854 school children (aged 12-18 years) of Bangladesh. Ten public high schools (five from Dhaka and five from Sirajgonj district) were selected randomly and subjects from those were recruited conveniently. To link the family milieu of CVD risk factors, a parent of each children was also interviewed. PRIMARY AND SECONDARY OUTCOME MEASURES: Distribution of CVD risk factors was measured using descriptive statistics as appropriate. Again, a saturated model of binary logistic regression was used to seek the association between place of residence and modifiable CVD risk factors. RESULTS: Mean age of the school children was 14.6±1.1 years and more than half (57.6%) were boys. Overall, 4.4% were currently smoker (urban-3.5%, rural-5.2%) with a strong family history of smoking (42.2%). Similar proportion of school children were identified as overweight (total 9.8%, urban 14.7%, rural 5%) and obese (total 9.8%, urban 16.8%, rural 2.8%) with notable urban-rural difference. More than three-fourth (80%) of them were physically inactive with no urban-rural variation. Only 2.4% consumed recommended fruits and/ or vegetables (urban-3.1%, rural-1.7%). In the adjusted model, place of residence had higher odds for having several modifiable CVD risk factors: current smoking (OR: 1.807, CI 0.872 to 3.744), inadequate fruits and vegetables intake (OR: 1.094, CI 0.631 to 1.895), physical inactivity (OR: 1.082, CI 0.751 to 1.558), overweight (OR: 3.812, CI 2.245 to 6.470) and obesity (OR: 7.449, CI 3.947 to 14.057). CONCLUSIONS: Both urban and rural school children of Bangladesh had poor CVD risk factors profile that demands further nation-wide large scale study to clarify the current findings more precisely.

Filociclovir Is a Potent In Vitro and In Vivo Inhibitor of Human Adenoviruses.

Human adenovirus (HAdV) infection is common in the general population and can cause a range of clinical manifestations, among which pneumonia and keratoconjunctivitis are the most common. Although HAdV infections are mostly self-limiting, infections in immunocompromised individuals can be severe. No antiviral drug has been approved for treating adenoviruses. Filociclovir (FCV) is a nucleoside analogue which has successfully completed phase I human clinical safety studies and is now being developed for treatment of human cytomegalovirus (HCMV)-related disease in immunocompromised patients. In this report, we show that FCV is a potent broad-spectrum inhibitor of HAdV types 4 to 8, with 50% effective concentrations (EC50s) ranging between 1.24 and 3.6 µM and a 50% cytotoxic concentration (CC50) of 100 to 150 µM in human foreskin fibroblasts (HFFs). We also show that the prophylactic oral administration of FCV (10 mg/kg of body weight) 1 day prior to virus challenge and then daily for 14 days to immunosuppressed Syrian hamsters infected intravenously with HAdV6 was sufficient to prevent morbidity and mortality. FCV also mitigated tissue damage and inhibited virus replication in the liver. The 10-mg/kg dose had similar effects even when the treatment was started on day 4 after virus challenge. Furthermore, FCV administered at the same dose after intranasal challenge with HAdV6 partially mitigated body weight loss but significantly reduced pathology and virus replication in the lung. These findings suggest that FCV could potentially be developed as a pan-adenoviral inhibitor.

Use of Remdesivir in the Management of COVID-19: A Systematic Review on Current Evidences.

The rapid progression of corona virus disease in 2019 (COVID-19) pandemic has become an unprecedented global concern. This systemic review aimed at evaluating the available evidence on efficacy, safety to identify any promising role for compassionate use of remdesivir in patient suffered for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE, Cochrane Library for randomized controlled trials (RCTs), prospective case series studies and case reports that evaluated use of remdesivir in COVID-19. The outcomes were mortality, recovery rate, length of hospital stay and clinical outcome. Though the drug remdesivir (RDV) is not approved by the FDA, still the "Emergency Use Authorization" (EUA) for compassionate use in severe cases is endorsed. After vigorous searching, screening and sorting of completed and published scientific evidences in electronic database, there were only 2 randomized control trial (RCT), 2 uncontrolled trials found until April 2020. We also included 3 published case reports to analyze the validity use of RDV because of the scarcity of evidence based reports. Remdesivir was thought to be one of the promising options for treating the patients of COVID-19 based on few laboratory experiments and reports from some compassionate use and case reports. The safety and efficacy of this drug in COVID-19 cases require high-quality evidence from well-designed and adequately-powered clinical trials with proper sample size for precise decision.

Thymoquinone-encapsulated chitosan nanoparticles coated with polysorbate 80 as a novel treatment agent in a reserpine-induced depression animal model.

Depression is a mental illness with a high prevalence in humans reaching 21% of the worldwide population.The present study aims to evaluate the antidepressant effect of different formulations of Thymoquinone; free Thymoquinone (TQ), Thymoquinone-loaded Chitosan nanoparticles (TQ-TPP-Cs NPs) and Thymoquinone-loaded Chitosan nanoparticles coated with polysorbate 80 (TQ-TPP-Cs NPs-PSb80) that have been prepared to avoid the low bioavailability of TQ. Rats were randomly separated into control rats, depression control induced by reserpine, rat model treated with TQ, rat model treated with TQ-TPP-Cs NPs and rat model treated with TQ-TPP-Cs NPs-PSb80. The results indicate that TQ-TPP-Cs NPs loaded with polysorbate 80 was more efficient in ameliorating the behavioral and neurochemical changes induced by reserpine than TQ and TQ-TPP-Cs NPs. Formulationswere characterized for size, morphology, encapsulation efficiency and in vitro drug release before their use in treatment. Reserpine induced a reduction in motor activity and swimming time and increased immobility time as indicated from the open field test (OFT) and forced swimming test (FST). In addition, a significant decrease in the monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE) and dopamine (DA) was recorded in the cortex, hippocampus and striatum of reserpine-treated rats. The present data suggest that the antidepressant efficacy of TQ could be enhanced by engaging TQ with chitosan nanoparticles as a drug carrier and the formulations were modified by coating with polysorbate 80.

Viral contamination in biologic manufacture and implications for emerging therapies.

Recombinant protein therapeutics, vaccines, and plasma products have a long record of safety. However, the use of cell culture to produce recombinant proteins is still susceptible to contamination with viruses. These contaminations cost millions of dollars to recover from, can lead to patients not receiving therapies, and are very rare, which makes learning from past events difficult. A consortium of biotech companies, together with the Massachusetts Institute of Technology, has convened to collect data on these events. This industry-wide study provides insights into the most common viral contaminants, the source of those contaminants, the cell lines affected, corrective actions, as well as the impact of such events. These results have implications for the safe and effective production of not just current products, but also emerging cell and gene therapies which have shown much therapeutic promise.

Safety of tympanoplasty and ossiculoplasty performed by otorhinolaryngology trainees.

OBJECTIVE: This study aimed to examine the impact of trainee involvement in performing tympanoplasty or tympano-ossiculoplasty on outcomes. METHODS: A retrospective analysis was performed of a prospective database of all patients undergoing tympanoplasty and tympano-ossiculoplasty in a single centre during a three-year period. Patients were divided into three primary surgeon groups: consultants, fellows and residents. The outcomes of operative time, surgical complications, length of hospital stay, and air-bone gap improvement were compared among the groups. RESULTS: The study included 398 tympanoplasty and tympano-ossiculoplasty surgical procedures, 71 per cent of which were performed by junior trainees (residents). The junior trainee group was associated with a significantly longer surgical time, without adverse impact on outcomes. CONCLUSION: Trainee participation in tympanoplasty and tympano-ossiculoplasty surgery was associated with longer surgical time, but did not negatively affect the peri-operative course or hearing outcome. Therefore, resident involvement in these types of surgery is safe.

The discovery and development of filociclovir for the prevention and treatment of human cytomegalovirus-related disease.

Human cytomegalovirus (HCMV) infections are widespread among the human population. Infection is persistent and mostly asymptomatic, except in immunocompromised individuals, particularly transplant patients, where significant morbidity and mortality can occur. Currently approved drugs for treating HCMV-related disease [including ganciclovir (GCV), valganciclovir (VGCV), cidofovir (CDV) and foscarnet (FOS)] all target the viral DNA polymerase and suffer from dose-limiting toxicity and resistance issues. The most recently approved drug, letermovir (LMV), was approved only for prophylaxis in adult HCMV-seropositive stem cell transplant recipients. Although LMV is highly potent, high-grade resistance mutations in the terminase gene were shown to readily emerge in vitro and in treated patients. Therefore, there is a need for new drugs that can be used for combinatorial therapeutic and/or prophylactic regimens to counteract the emergence of resistant mutants. Filociclovir (FCV), also known as cyclopropavir or MBX-400, is a methylenecyclopropane nucleoside analog, which has successfully completed Phase I safety studies, and is now entering Phase II clinical efficacy studies for the treatment of HCMV-related disease in transplant patients. FCV is 10-fold more active than GCV against HCMV in vitro, and has activity against all human herpesviruses except HSV-1 and HSV-2. Recently, FCV was also shown to be highly potent against human adenoviruses. This activity spectrum suggests that FCV could be used to treat/prevent infection with several viruses that pose significant risk to transplant patients. The active triphosphate form of FCV (FCV-TP) reaches higher peak levels than GCV-TP in HCMV-infected cells, and exhibits about 10-fold higher affinity to HCMV DNA polymerase UL54. Furthermore, FCV was shown to retain activity against a panel of GCV-resistant HCMV isolates, suggesting that it could be a useful alternative therapy for treating patients infected with some GCV-resistant HCMV strains. This review summarizes the early discovery work of FCV and highlights the recent advances in the continued development of this clinical candidate.