The Regulator Dependent SemiTargeted Approach to Switch on Muted Biosynthetic Gene Clusters

Propionic Acidemia (PA) is an inborn error of metabolism caused by variants in the PCCA or PCCB genes, leading to mitochondrial accumulation of propionyl-CoA and its by-products. Here, we report a 2 year-old Egyptian boy with PA who was born to consanguineous parents. Biochemical analysis was performed using tandem mass spectrometry (MS/MS) on the patient's dried blood spots (DBS) followed by urine examination of amino acids using gas chromatography/mass spectrometry (GC/MS). Molecular genetic analysis was carried out using whole-exome sequencing (WES). The PCCA gene sequencing revealed a novel homozygous missense variant affecting the locus (chr13100962160) of exon 16 of the PCCA gene, resulting in the substitution of the amino acid arginine with proline at site 476 (p.Arg476Pro). Computational analysis revealed that the novel variant might be pathogenic and attributed to decrease the stability and also has an effect on the biotin carboxylase c-terminal domain of the propionyl carboxylase enzyme. The physicochemical properties analysis using NCBI amino acid explorer study revealed restrictions in the side chain and loss of hydrogen bonds due to the variant. On the structural level, the loss of beta-sheet was observed due to the variant proline, which has further led to the loss of surrounding interactions. This loss of beta-sheet and the surrounding interactions might serve the purpose of the structural stability changes. The current study demonstrates that a combination of whole-exome sequencing (WES) and computational analysis are potent tools for validation of diagnosis and classification of disease-causing variants.Medullary sponge kidney (MSK) is a characteristic renal malformation, with a relatively low incidence. Radiologically, identification of MSK is sometimes ambiguous when compared to a renal mass. Here, we report a novel renal clear cell carcinoma in MSK, and discuss our approach to treatment. We recommended that a preoperative biopsy should be performed, followed by a comprehensive discussion regarding the appropriate perioperative preparations and careful surgical techniques that should be performed for this complex disease.
Novel optical imaging modalities are under development with the goal of obtaining an "optical biopsy" to efficiently provide pathologic details. One such modality is confocal microscopy which allows
visualization of cells within a layer of tissue and imaging of cellular-level structures. The goal of this study is to validate the ability of confocal microscopy to quickly and accurately differentiate between normal renal tissue and cancer.
Specimens were obtained from patients who underwent robotic partial nephrectomy for renal mass. Samples of suspected normal and tumor tissue were extracted from the excised portion of the kidney and stained with acridine orange. The stained samples were imaged on a Nikon E600 C1 Confocal Microscope. The samples were then submitted for hematoxylin and eosin processing and read by an expert pathologist to provide a gold-standard diagnosis that can later be compared to the confocal images.
This study included 11 patients, 17 tissue samples, and 118 confocal images. Of t high sensitivity and specificity. The observers in this study were trained quickly and on only six images. We expect even higher performance as observers become more familiar with the confocal images.
The Polaris™ loop ureteric stent reduces the severity of stent discomfort by minimising stent material in the bladder. Early impact of ureteral stenting on quality of life (QoL) within 1 week remains unclear. The usefulness of the patient-administered ureteral stent symptoms questionnaire (USSQ) during this period of stent insertion was assessed. In this pilot single-blinded prospective randomised study, we investigate 1) the presence of early (within the 1st week) stent discomfort via the visual analog scale (VAS); 2) determine the QoL of the loop stent against conventional stent.
Forty adults requiring retrograde unilateral ureteral stent placements were enrolled. Patients with single ureteric stone or benign stricture were selected. Patients were randomised in 11 ratio to the loop and pigtail arm. The USSQ was administered before placement (baseline), USSQ and VAS were administered on Day 3, 7, and 14.
There were no significant differences between the USSQ scores. Median pain scores on Day 3 were lower in the loop stent group (2.9
4.0,
=0.047). There was a significant reduction in pain from Day 3-7 (0
-1,
=0.016) in the pigtail group.
Our results suggest that peak stent discomfort occurs but resolves quickly within 1 week of post-stent insertion. The loop stent offers a better pain profile compared with conventional stents at Day 3 but no difference in QoL. The loop stent reduces early pain experience post-stent insertion and may have a role in the care of patients who experience significant stent discomfort previously.
Our results suggest that peak stent discomfort occurs but resolves quickly within 1 week of post-stent insertion. The loop stent offers a better pain profile compared with conventional stents at Day 3 but no difference in QoL. find more The loop stent reduces early pain experience post-stent insertion and may have a role in the care of patients who experience significant stent discomfort previously.
Two conventional approaches for vesicovaginal fistula (VVF) repair are transabdominal repair for supratrigonal VVF and transvaginal approach for low lying fistulae. Laparoscopic surgery was introduced to duplicate the surgical steps of the transabdominal approach with reduction in morbidity. We report a series of patients treated with a modified laparoscopic technique which includes the use of only three trocars and a limited posterior cystotomy.
We retrospectively reviewed the data of eight patients who underwent laparoscopic VVF repair with our standardized technique from January 2015 to April 2018. Only cases with a supratrigonal fistula were included. We constantly used only three trocars. A limited 2cm midline posterior cystotomy was performed using ultrasonic energy. A stay suture on a straight needle was passed percutaneously in the abdomen, then on either side of the cystotomy and finally was exteriorized to maintain countertraction. The cystotomy was extended downwards to include the fistula site.