Genetic deregulation of the PIK3CA oncogene in oral cancer

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is one of the most commonly deregulated pathways in human cancers. PI3K comprises a catalytic (p110α) and regulatory subunit (p85), and p110α is encoded by the PIK3CA gene. Here, we summarize the known genetic alterations, including amplifications and mutations, of the PIK3CA oncogene in oral cancer. We discuss in detail PIK3CA mutations and their mutual exclusivity with pathway genes in addition to the incidence of PIK3CA mutations in relation to ethnicity. We describe the constitutive activation of PI3K signaling, oncogenicity, and the genetic deregulation of the PIK3CA gene and its association with oral cancer disease stage. We emphasize the importance of therapeutically targeting the genetically deregulated PIK3CA oncogene and its signaling. We also discuss the implications of targeting Akt and/or mTOR, which are the downstream effectors of PI3K that may possibly pave the way for molecular therapeutic targets for PIK3CA-driven oral carcinogenesis. Furthermore, this critical review provides a complete picture of the PIK3CA oncogene and its deregulation in oral cancer, which may facilitate early diagnosis and improve prognosis through personalized molecular targeted therapy in oral cancer.     

Loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia in HIV-uninfected immunocompromised patients with pulmonary infiltrates

Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-β-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2–3 days; n = 10) was shorter than in subcontract PCR group (7; 7–12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment.     

C-MET is expressed in the majority of penile squamous cell carcinomas and correlates with polysomy-7 but is not associated with MET oncogene amplification,pertinent histopathologic parameters,or with cancer-specific survival

We assessed c-MET expression and oncogene amplification in a cohort enrolling 92 surgically treated penile squamous cell carcinomas (PSCCs). A tissue microarray was constructed for c-MET immunohistochemistry (IHC) and chromogenic silver in situ hybridization (SISH). Two independent pathologists evaluated IHC by employing the breast cancer scoring rules, and scored the presence of MET oncogene amplification and/or polysomy-7. Eighty study cases (87%) showed c-MET expression. No study case had MET oncogene amplification, but 42 patients (45.7%) had polysomy-7. Polysomy-7 showed a significant positive correlation with c-MET expression (ρ = 0.323, p = 0.002). Neither c-MET expression nor polysomy-7 was associated with histopathologic parameters or with cancer-specific survival (median post-surgical follow-up 32 months). Our data suggest that the majority of PSCCs exhibit c-MET expression which is not associated with oncogene amplification, but might be attributable to polysomy-7. Further studies should investigate the expression and activation of downstream molecules functionally involved in c-MET pathway signaling, and clarify the so far unresolved role of c-MET inhibitors as potential targeted therapies in PSCCs with metastatic dissemination.     

Successful reproduction of adenoviral gizzard erosion in 20-week-old SPF layer-type chickens and efficacious prophylaxis due to live vaccination with an apathogenic fowl adenovirus serotype 1 strain (CELO)

Recently, outbreaks of adenoviral gizzard erosion (AGE) have been documented in pullets and layers housed free range and in enriched cage systems characterized by increased mortality and a negative impact on egg production. In the present study the pathogenicity of a fowl adenovirus serotype 1 (FAdV-1) field strain as well as the aetiological role of a FAdV-8a strain, both isolated from AGE affected pullets, were investigated in vivo in 20-week-old specific-pathogen-free (SPF) layer-type chickens. Furthermore, the efficacy of a single (week 17) and double (week 14 and 17) application of a live vaccine consisting of an apathogenic FAdV-1 (CELO strain) against challenge with virulent FAdV-1 was investigated.For the first time, AGE was successfully reproduced in adult birds after oral infection of 20-week-old SPF birds with a virulent FAdV-1 field isolate, characterized by pathological changes of the gizzard from 7 days post challenge onwards. In addition, a negative impact of the FAdV-1 infection on the development of the reproductive tract was observed. Thus, confirming the pathogenicity and aetiological role of FAdV-1 in the development of AGE and economic losses due to AGE in layers. In contrast, no pathological changes were observed in birds infected with FAdV-8a.Independent of a single or double application of the live FAdV-1 vaccine strain CELO, no gross pathological changes were observed in gizzards post challenge with the virulent FAdV-1, indicating that complete protection of layers against horizontal induction of AGE was achieved. Nonetheless, virulent FAdV-1 was detected in cloacal swabs and gizzards in both vaccinated groups post challenge determined by the application of an amplification refractory mutation system quantitative PCR used to differentiate between vaccine and challenge strains.     

Wireless Connectivity for People with Hearing Loss: Argumentum ad Ignorantiam: Smartphone-Connected Listening Devices

In this article, we review the current literature assessing the application and benefits of connected hearing technologies, as well as their potential to improve accessibility to and affordability of hearing healthcare. Over the past decade, there has been a proliferation of hearing devices that connect wirelessly to smartphone technologies via Bluetooth. These devices include (1) smartphone-connected hearing aids that must be obtained from a licensed audiologist or hearing aid dispenser; (2) direct-to-consumer devices, such as personal sound amplification products; and (3) smartphone-based hearing aid applications (or apps). Common to all these connected devices is that they permit the user to self-adjust and customize their device programs via an accompanying smartphone app. There has been a growing body of literature assessing connected hearing devices in adults living with hearing loss. Overall, the evidence to date supports the notion that all connected hearing devices can improve accessibility to and affordability of amplification. It is unclear, however, whether connected technologies are a clinically effective alternative to traditional hearing aids. Even so, the impact of connectivity is especially pertinent given the sudden disruption caused by the recent global COVID-19 pandemic, whereby connected technologies enable patients to receive treatment through mobile-based, tele-audiology platforms.     

Gonorrhoea diagnostics: An update

Diagnosis of gonorrhoea is an ongoing challenge. The organism is fastidious requiring meticulous collection and transport for successful cultivation. Asymptomatic infections are common which go undetected by conventional methods thereby leading to continued transmission and the risk of complications. The nucleic acid amplification tests, now increasingly used in developed countries, offer improved sensitivity compared to bacterial culture. However, these continue to suffer sequence related problems leading to false positive and false negative results. Further, these cannot be used for generation of data on antibiotic susceptibility because genetic markers of antibiotic resistance to recommended therapies have not been fully characterised. They are unaffordable in a setting like ours where reliance is placed on syndromic approach for sexually transmitted infection (STI) management. The use of syndromic approach has resulted in a considerable decline in the number of Neisseria gonorrhoeae isolates that have been cultured for diagnostic purposes. Many laboratories formerly doing so are no longer performing culture for gonococci, and the basic skills have been lost. There is a need to not only revive this skill but also adopt newer technologies that can aid in accurate diagnosis in a cost-effective manner. There is room for innovation that can facilitate the development of a point-of-care test for this bacterial STI.     

Recent progress on the diagnosis of 2019 Novel Coronavirus

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic. Therefore, convenient, timely and accurate detection of SARS‐CoV‐2 is urgently needed. Here, we review the types, characteristics and shortcomings of various detection methods, as well as perspectives for the SARS‐CoV‐2 diagnosis. Clinically, nucleic acid‐based methods are sensitive but prone to false‐positive. The antibody‐based method has slightly lower sensitivity but higher accuracy. Therefore, it is suggested to combine the two methods to improve the detection accuracy of COVID‐19.