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A 75-year-old man was referred to our urology service with painless haematuria. The delayed phase on a subsequent computed tomography (CT) abdomen and pelvis showed a filling defect in the left renal pelvicalyceal system, suspicious for a transitional cell carcinoma. The patient underwent ureteroscopic biopsy suggestive of a papillary neoplasia, before progressing to a laparoscopic radical left nephrouretectomy. Final histology revealed a fumarate hydratase-deficient renal cell carcinoma with clear margins. The patient was subsequently referred for genetic counselling.

A 55-year-old male presented to our emergency department with haematuria and abdominal pain. Investigations including a computed tomography (CT) scan revealed an intraluminal filling defect within the left collecting system, consistent in appearance with blood clot. With an initial working diagnosis of upper tract urothelial cell carcinoma, he was discharged with plans for an urgent cystoscopy and ureteroscopy. He subsequently represented with ongoing frank haematuria, anasarca, dropping haemoglobin and new right collecting system blood clot. Subsequent investigations showed that the patient had acquired haemophilia A resulting in the episodes of haematuria, highlighted after an elevated activated partial thromboplastic time prompted a thrombophilia screen. The patient was subsequently treated with factor eight inhibitor bypass activity, corticosteroids and cyclophosphamide.

The number of Australian patients undergoing ventral hernia repair has seen a significant increase in the last twenty years. With the obesity epidemic, the general surgeon is frequently seeing patients with hernias and significant abdominal aprons and is being asked to address this at the time of the hernia repair. This can be performed utilising a general surgery and plastic surgery team, but there may be some advantages to general surgeon being able incorporate this into their practice. We present our approach to patients undergoing ventral hernia repair and simultaneous panniculectomy (VHR + PAN) by a single general surgeon. Data were analysed from a single surgeon’s experience performing VHR + PAN at the same operation. Data were collected prospectively from 2009 to 2020. 146 cases of patients undergoing VHR + PAN were identified and included in this study. The mean age of patients undergoing VHR + PAN was 58 years. The mean BMI was 35, with 59% of patients losing weight loss prior to surgery. 66% of patients had a hernia repair with biosynthetic mesh and 91% of patients had retro-rectus or pre-peritoneal mesh approach to the repair. 42% of patients had a post-operative complication with 80.6% of these being related to surgical-site occurrences. Other complications included gastrointestinal (14%), respiratory (13%) and venous thromboembolism, such as a deep vein thrombus or pulmonary embolism (6%). There were 2 deaths in the series (1.3%). The hernia recurrence rate was 6%. Simultaneous PAN is possible in patients with an abdominal apron who are undergoing VHR, with an acceptable risk of SSOs and other complications. This technique provides excellent exposure and with appropriate training is well within the remit of the general surgeon. This may save further operative management in the future and can offer patients improved self-esteem, mobility, and independence. Patient optimisation is key, paying careful attention to pre-operative weight loss, diabetic control, smoking cessation and respiratory function. VHR + PAN is an important technique that should be in the repertoire of all abdominal wall reconstruction units.

Transposable elements (TEs) are a reservoir of new transcription factor binding sites for protein-coding genes1–3. Developmental programs that activate TE-derived regulatory elements could, in principle, manifest in lineage-specific TE mobility. While somatic LINE-1 (L1) retrotransposon insertions have been detected in human neurons4–6, the impact of L1 insertions on neurodevelopmental gene regulation, and whether L1 mobility is restricted to certain neuronal lineages, is unknown. Here, we reveal programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV+) interneuron development7–9. PV+ neurons harbor unmethylated and euchromatic L1 promoters, express L1 mRNA, and permit L1 transgene mobilization in vivo. Elevated L1 expression in adult dentate gyrus PV+ neurons is however attenuated by environmental enrichment. Nanopore sequencing of PV+ neurons identifies unmethylated L1 loci providing alternative promoters to core PV+ neuron genes, such as CAPS2. These data depict SOX6-mediated L1 activation as an ingrained component of the mammalian PV+ neuron developmental program.

The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic diversity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the divergence of apes and Old World monkeys, successive L1 subfamilies have emerged in each descendant primate germline. As revealed by case studies, the presently active human L1 subfamily can also mobilize during embryonic and brain development in vivo. It is unknown whether nonhuman primate L1s can similarly generate somatic insertions in the brain. Here we applied approximately 40× single-cell whole-genome sequencing (scWGS), as well as retrotransposon capture sequencing (RC-seq), to 20 hippocampal neurons from two rhesus macaques (Macaca mulatta). In one animal, we detected and PCR-validated a somatic L1 insertion that generated target site duplications, carried a short 5′ transduction, and was present in ∼7% of hippocampal neurons but absent from cerebellum and nonbrain tissues. The corresponding donor L1 allele was exceptionally mobile in vitro and was embedded in PRDM4, a gene expressed throughout development and in neural stem cells. Nanopore long-read methylome and RNA-seq transcriptome analyses indicated young retrotransposon subfamily activation in the early embryo, followed by repression in adult tissues. These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a nonhuman primate, and allude to L1 mobility in the brain over the past 30 million years of human evolution.

Amyloidosis of the lower genitourinary tract is an extremely rare condition and often mimics urothelial malignancy. In this paper, we report two cases of ureteral and urethral amyloidosis that initially presented as urothelial carcinoma and were successfully treated with laparoscopic nephroureterectomy and trans-urethral resection, respectively. This disease, with its various atypical presentations, presents a diagnostic challenge to urologists. Awareness is important as excision can be curative, and presence of systemic disease must be excluded.

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus., Graphical abstract, In response to a recent claim that SARS-CoV-2 can be incorporated into human DNA by LINE-1 retrotransposon proteins, Smits et al. apply long-read DNA sequencing to cultured HEK293T cells infected with SARS-CoV-2. They find no evidence for genomic integration of the virus, despite demonstrated availability of the LINE-1 protein machinery.

SUMMARYA recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolved 78 L1 insertions arisingin vitroin the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events are, at most, extremely rarein vivo, and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.

The number of Australian patients undergoing ventral hernia repair has seen a significant increase in the last twenty years. With the obesity epidemic, the general surgeon is frequently seeing patients with hernias and significant abdominal aprons and is being asked to address this at the time of the hernia repair. This can be performed utilising a general surgery and plastic surgery team, but there may be some advantages to general surgeon being able incorporate this into their practice. We present our approach to patients undergoing ventral hernia repair and simultaneous panniculectomy (VHR + PAN) by a single general surgeon.Data were analysed from a single surgeon's experience performing VHR + PAN at the same operation. Data were collected prospectively from 2009 to 2020. 146 cases of patients undergoing VHR + PAN were identified and included in this study.The mean age of patients undergoing VHR + PAN was 58 years. The mean BMI was 35, with 59% of patients losing weight loss prior to surgery. 66% of patients had a hernia repair with biosynthetic mesh and 91% of patients had retro-rectus or pre-peritoneal mesh approach to the repair. 42% of patients had a post-operative complication with 80.6% of these being related to surgical-site occurrences. Other complications included gastrointestinal (14%), respiratory (13%) and venous thromboembolism, such as a deep vein thrombus or pulmonary embolism (6%). There were 2 deaths in the series (1.3%). The hernia recurrence rate was 6%.Simultaneous PAN is possible in patients with an abdominal apron who are undergoing VHR, with an acceptable risk of SSOs and other complications. This technique provides excellent exposure and with appropriate training is well within the remit of the general surgeon. This may save further operative management in the future and can offer patients improved self-esteem, mobility, and independence. Patient optimisation is key, paying careful attention to pre-operative weight loss, diabetic control, smoking cessation and respiratory function. VHR + PAN is an important technique that should be in the repertoire of all abdominal wall reconstruction units.

Level of evidence: IV

Purpose The changing dynamics of an aging mouth influence the position of the neutral zone (NZ). While the advantage of the NZ concept in complete denture treatment is quite established, what is not clearly understood is its position in relation to the crest of the residual ridge due to conflicting reports from previous studies. The purpose of this study was to investigate the distance and direction of NZ position in relation to crest of the residual ridge in edentulous patients and its association with age, gender, and period of edentulism. Materials and Methods A cross-sectional study was conducted in 133 patients (70 males, 63 females) with a mean age of 58.81 ± 11.78 years. NZ recording was done using admix material by following standard procedures. Two metallic wires were adapted, one on the ridge and another on the center of the occlusal rims, and standardized digital radiographs were made. The position of NZ in relation to the crest of the residual ridge was recorded by noting the direction and measuring the distance between the adapted wires digitally at five locations (right molar, right premolar, incisor, left molar, left premolar regions). Results Age, gender, and period of edentulism had no significant association with the position of NZ. No specific trend was observed in the in NZ position with a non-significant correlation. Conclusions Distance and the direction of neutral zone position in relation to crest of the residual ridge in edentulous patients bear no significant relationship with factors such as age, gender, and period of edentulism.

Biological sequences are an important part of global patenting, with unique challenges for their effective and equitable use in practice and in policy. Because their function can only be determined with computer-aided technology, the form in which sequences are disclosed matters greatly. Similarly, the scope of patent rights sought and granted requires computer readable data and tools for comparison. Critically, the primary data provided to the national patent offices and thence to the public, must be comprehensive, standardized, timely and meaningful. It is not yet. The proposed global Patent Sequence (PatSeq) Data platform can enable national and regional jurisdictions meet the desired standards.

This study aims to determine the functional roles of microRNA-34b-5p (miR-34b) in the suppression of anaplastic thyroid carcinoma. We used hydration-of-freeze-dried-matrix (HFDM) formulated liposomes (liposome-loaded miR-34b) for effective delivery of miR-34b to anaplastic thyroid carcinoma in vitro and in vivo. Real time polymerase chain was used to determine the level of miR-34b. Immunocytochemistry, Western blot and ELISA were carried out to determine the effect of this manipulation on VEGF-A expression. In addition, an in vivo xenotransplantation mouse model was used to investigate the functional roles of overexpression of miR-34b in the carcinoma. In anaplastic thyroid carcinoma cells, miR-34b expression was low and significant overexpression (p &lt, 0.05) was noted following transfection with liposome-loaded miR-34b. The miR-34b overexpressed thyroid carcinoma cell lines showed reduction in VEGF-A protein expression, decreased cell proliferation, decreased wound healing, reduced cell cycle progression and increased apoptosis (p &lt, 0.05). In in vivo experiments, when compared to control groups, smaller tumours formed upon intravenous administration of liposome-loaded miR-34b. To conclude, the current study confirmed the tumour suppressor properties of miR-34b via VEGF-A regulation in anaplastic thyroid carcinoma. In addition, delivery of miR-34b using cationic liposome could be a useful therapeutic strategy for targeting therapy in the carcinoma.

The changing dynamics of an aging mouth influence the position of the neutral zone (NZ). While the advantage of the NZ concept in complete denture treatment is quite established, what is not clearly understood is its position in relation to the crest of the residual ridge due to conflicting reports from previous studies. The purpose of this study was to investigate the distance and direction of NZ position in relation to crest of the residual ridge in edentulous patients and its association with age, gender, and period of edentulism.A cross-sectional study was conducted in 133 patients (70 males, 63 females) with a mean age of 58.81 ± 11.78 years. NZ recording was done using admix material by following standard procedures. Two metallic wires were adapted, one on the ridge and another on the center of the occlusal rims, and standardized digital radiographs were made. The position of NZ in relation to the crest of the residual ridge was recorded by noting the direction and measuring the distance between the adapted wires digitally at five locations (right molar, right premolar, incisor, left molar, left premolar regions).Age, gender, and period of edentulism had no significant association with the position of NZ. No specific trend was observed in the in NZ position with a non-significant correlation.Distance and the direction of neutral zone position in relation to crest of the residual ridge in edentulous patients bear no significant relationship with factors such as age, gender, and period of edentulism.

The gastrointestinal tract represents the largest immune interface with the environment. Exposure to large numbers of dietary and microbial antigens requires complex and highly regulated intestinal immune responses by different immune cell types for the maintenance of oral tolerance. Defective immune homeostasis can cause gut barrier dysfunction and breakdown of tolerance, leading to chronic inflammation and autoimmunity. In this review, we summarize the key immune cell populations involved in oral tolerance. We also describe diet-modifiable aspects of gut immunity that alter the intricate balance between inflammatory and tolerogenic immune responses in the gut and contribute to disease development.

Complementation of movement and coat proteins of the orchid-infecting potexvirus Cymbidium mosaic virus (CymMV) and tobamovirus Odontoglossum ringspot virus (ORSV) was investigated. Nicotiana benthamiana, which is susceptible to both CymMV and ORSV, was used as a model system. Four transgenic lines, each harbouring one of the movement protein (MP) or coat protein (CP) genes of CymMV or ORSV, were constructed. The MP of CymMV consists of three overlapping open reading frames, together called the triple-gene block (TGB). CymMV and ORSV mutants, each carrying an inactivated MP or CP, were generated from the respective biologically active full-length cDNA clones. Complementation was studied by infecting transgenic plants with in vitro transcripts generated from these mutants. The cell-to-cell movement of a movement-deficient CymMV was restored in transgenic plants carrying the ORSV MP transgene. Similarly, CymMV TGB1 transgenic plants were able to rescue the cell-to-cell movement of a movement-deficient ORSV mutant. ORSV CP transgenic plants supported systemic movement of a CymMV CP-deficient mutant. However, in these plants, neither encapsidation of CymMV RNA with ORSV CP nor CymMV CP expression was detected. Long-distance movement of an ORSV CP-deficient mutant was not supported by CymMV CP. The complementation of MPs and CPs of CymMV and ORSV facilitates movement of these viruses in plants, except for long-distance movement of ORSV RNA by CymMV CP.

The variability in coat protein gene sequences of Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) that naturally infect orchids worldwide was investigated. Samples were collected from Korea, Singapore and Taiwan. The sequence data were compared with available published coat protein gene sequences of CymMV and ORSV, including those from Japan and Thailand. Among CymMV isolates, the homology was 89.1%-99.7% and 93.2%-100% at the nucleotide and amino acid levels, respectively. Among the ORSV isolates, the homology was 95.5%-100% and 93%-100% at the nucleotide and amino acid levels, respectively. No particular region of variability could be defined in either of the viruses. In deduced amino acid sequence, the N-terminal was more conserved than the C-terminal in both CymMV and ORSV. By comparing all sequences determined in this study and those that are published in the GenBank databases, we did not find clustering based on geographical distribution or sequence identity. Such high sequence conservation suggests that both CymMV and ORSV coat protein genes are suitable candidates to provide resistance to orchids cultivated in different geographical locations.