Transurethral water vapour thermal therapy for benign prostatic hyperplasia under local anaesthesia alone: initial experience in Chinese patients.

INTRODUCTION: This study evaluated the perioperative and early postoperative outcomes of transurethral water vapour thermal therapy (WVTT) under local anaesthesia alone for benign prostatic enlargement in Chinese patients. METHODS: This retrospective review of transurethral WVTT for benign prostatic enlargement focused on 50 Chinese patients who exhibited clinical indications (acute retention of urine or symptomatic lower urinary tract symptoms due to benign prostatic enlargement) for surgical treatment between June 2020 and December 2021 in Hong Kong. Exclusion criteria included active urinary tract problems and urological malignancies. Follow-up was conducted at 3 months postoperatively. RESULTS: The median patient age was 71.5 years. The mean preoperative prostatic volume was 56.7 mL. The mean operation time was 25.1 minutes. All procedures were performed under local anaesthesia alone. The mean pain scores for transrectal ultrasound probe insertion, transperineal local anaesthesia injection, and transurethral WVTT were 2, 5, and 4, respectively. Forty-nine patients (98%) were discharged on the same day with a urethral catheter. Forty-eight patients (96%) successfully completed a trial without catheter within 3 weeks postoperatively. Five patients (10%) had unplanned hospital admission within 30 days postoperatively due to surgical complications (Clavien-Dindo grade 1). CONCLUSION: Transurethral WVTT, an advanced surgical treatment for benign prostatic enlargement, is a safe procedure that relieves lower urinary tract symptoms with minimal hospital stay. It can be performed in an office-based setting under local anaesthesia, maximising utilisation of the surgical theatre.

Public awareness of preventive measures against COVID-19: an infodemiology study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to an increase in global awareness of relevant public health preventive measures. This awareness can be explored using online search trends from major search engines, such as Google Trends. We investigated the relationship between public awareness of preventative measures and progression of the COVID-19 pandemic. METHODS: Search data for five queries ('mask', 'hand washing', 'social distancing', 'hand sanitizer', and 'disinfectant') were extracted from Google Trends in the form of relative search volume (RSV). Global incidence data for COVID-19 were obtained from 1 January to 30 June 2020. These data were analysed and illustrated using a global temporal RSV trend diagram, a geographical RSV distribution chart, scatter plots comparing geographical RSV with average number of daily cases, and heat maps comparing temporal trends of RSV with average number of daily cases. RESULTS: Global temporal trends revealed multiple increases in RSV, associated with specific COVID-19-related news events. The geographical distribution showed top regions of interest for various preventive measures. For the queries 'mask', 'hand washing', 'hand sanitizer', and 'disinfectant', heat maps demonstrated patterns of early RSV peaks in regions with lower average number of daily cases, when the temporal element was incorporated into the analysis. CONCLUSION: Early public awareness of multiple preventive measures was observed in regions with lower average number of daily cases. Our findings indicate optimal public health communication regarding masks, hand washing, hand sanitiser, and disinfectant in the general population during early stages of the COVID-19 pandemic. Early public awareness may facilitate future disease control efforts by public health authorities.

Potential effects of COVID-19 on reproductive systems and fertility; assisted reproductive technology guidelines and considerations: a review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the angiotensin-converting enzyme 2 (ACE2) receptor in the renin-angiotensin system for viral entry. The ACE2 receptor is present in both female and male reproductive systems, and reports of multi-organ involvement have led to uncertainty regarding its effects on the reproductive system and fertility. We review the existing literature regarding the function of ACE2 and the renin-angiotensin system in the female and male reproductive systems to postulate the possible implications of SARS-CoV-2 regarding fertility. Because of the presence of ACE2 in the ovaries, SARS-CoV-2 infection may disrupt ovarian function and hence oocyte quality. Higher expression of ACE2 in the endometrium with age and during the secretory phase raises concern about increased susceptibility to infection during periods of high ACE2 expression. The possibility of vertical transmission and the presence of ACE2 in the placenta and during pregnancy are also discussed. The presence of SARS-CoV-2 RNA in semen is controversial, but impaired semen quality has been found in men with moderate coronavirus disease 2019 infection. Evidence of orchitis and hormonal changes seen in male coronavirus disease 2019 infection may lead to infertility. The implications of these effects on assisted reproductive technology (ART) outcomes are also explored. The ART guidelines from different fertility societies for the management of patients treated with ART are provided. The importance of prioritising 'time-sensitive' patients for ART, counselling patients about the uncertainty and risks of ART, and pregnancy during the pandemic is discussed. Recommendations are also provided for infection control and safe regulation of ART centres and laboratories.

Calcium influx differentially regulates migration velocity and directedness in response to electric field application.

Neural precursor cells (NPCs) respond to externally applied direct current electrical fields (DCEFs) by undergoing rapid and directed migration toward the cathode in a process known as galvanotaxis. It is unknown if the underlying mechanisms of galvanotactic migration is common to non-electrosensitive cells and if so, how NPCs and other galvanotactic cells sense and transduce electrical fields into cellular motility. In this study, we show that distinct aspects of NPC galvanotactic migration: motility (quantified through |velocity|) and directedness, are differentially regulated by calcium. We use low-Ca2+ culture conditions; an intracellular Ca2+ chelator; and voltage gated calcium channel (VGCC) inhibitors to specific channels expressed on NPCs, to demonstrate the role of Ca2+ influx in DCEF-induced NPC migration. Consistent with existing literature, we show Ca2+ is involved in F-actin polymerization that lengthens NPC membrane protrusions necessary for cellular motility. However, inhibiting Ca2+ results in reduced velocity but has no effect on DCEF-induced directedness. This dissociation between velocity and directedness reveal that these migration parameters can be independently regulated, thus suggesting a parallel process of sensing DCEFs by NPCs.

Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy.

Activity-dependent neuroprotective protein (ADNP) was shown to be essential for embryogenesis and brain development while NAP, an active motif of ADNP, is neuroprotective in a broad range of neurodegenerative disorders. In the present study, we examined the protective potential of ADNP/NAP in a mouse model of excitotoxic brain lesion mimicking brain damage associated with cerebral palsy. We demonstrated that NAP had a potent neuroprotective effect against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice, and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP appears not to be involved in the response to excitotoxic challenge in the studied model. Our findings further show that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented ibotenate-induced loss of pre-oligodendrocytes without affecting the number of astrocytes or activated microglia around the site of injection. These findings indicate that protective actions of NAP are mediated by triggering transduction pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP might be a promising therapeutic agent for treating developing brain damage.

Quality of life in patients with transfusion-dependent thalassemia after hematopoietic SCT.

In this cross-sectional study, we compared the quality of life (QOL) in transfusion-dependent thalassemic patients who survived matched sibling hematopoietic SCT (HSCT, n=24) with patients treated conventionally with transfusion and iron chelation (n=74). WHOQOL-BREF(HK) and PedsQL questionnaires were administered to patients aged >18 years and 5-12 years, respectively. Patients aged 12-18 years received both questionnaires. WHOQOL-BREF(HK) revealed post transplant patients rated overall health better than those treated conventionally (score 3.67 vs 3.06, P=0.01). They are less dependent on medical aids (3.87 vs 2.96, P=0.006), having higher activity level (4.00 vs 3.36, P=0.026) and better personal relationships (4.13 vs 3.69, P=0.014). Physical health domain score was better (75.20 vs 63.94, P=0.007). These differences remained significant after adjustment for comorbidities. PedsQL revealed post transplant patients rated better for running (3.53 vs 2.72, P=0.001) and sports (3.20 vs 2.64, P=0.038), even after adjustment for comorbidities, but were less satisfied for school absence to attend hospital (2.53 vs 3.29, P=0.03). Post transplant patients were significantly more likely to consider marriage (100 vs 75.7%, P=0.033), but not childbearing (66.7 vs 51.4%, P=0.28). In conclusion, transplanted thalassemic patients enjoy better QOL, mainly in physical health, compared with conventionally treated patients. This information is important to patients considering HSCT.

Three-month change in cerebral glucose metabolism in patients with nonarteritic ischemic optic neuropathy.

BACKGROUND: No specific therapy is available for non-arteritic ischemic optic neuropathy (NAION), a blinding disease, which is related to microvascular insufficiency of the optic disc and white matter lesions in brain MRI representing ischemia. We hypothesize that pentoxifylline, traditionally used for treatment of peripheral vascular disease due to its ability to decrease viscosity and increase erythrocyte flexibility, may be useful to improve blood flow in patients with NAION. Positron emission tomography (PET) to determine the change in glucose metabolic rate in the visual cortex of patients with NAION versus age-matched controls was performed after 3 months' administration of pentoxifylline. METHODS: Eight patients clinically diagnosed with NAION underwent clinical and laboratory evaluation, brain MRI and PET with fluoride-18 fluorodeoxyglucose (FDG). All patients were treated with oral pentoxifylline 400 mg three times a day for a period of at least 3 months. Three patients were included in the final PET data analysis. RESULTS: At baseline, PET revealed bilateral metabolic decreases especially in the ventral visual stream in all patients compared with 56 age- and gender-normalized controls. Metabolic changes were seen in the dorsal stream areas 17, 18, and 19, cerebellar region, dorsolateral prefrontal cortex, medial temporal lobe, and frontal eye fields 8 and 6. At 3 months following pentoxifylline, all three patients included in the final PET data analysis showed partial normalization from the baseline metabolism. CONCLUSIONS: Metabolic imaging with FDG-PET in NAION provides functional information not attainable with conventional brain MRI. The exact relevance of these results, and the role of pentoxifylline in these metabolic changes, should be determined by means of a larger randomized and controlled trial.

Increased expression of insulin-like growth factors in progressive glomerulonephritis of the MRL/lpr mouse.

Glomerulonephritis is an important complication of systemic lupus erythematosus (SLE). The tissue distribution and exact role of the insulin-like growth factors (IGFs) in the development of lupus nephritis in the MRL/lpr mouse model have not been established. The present study was undertaken to evaluate the changes over time in mRNA and peptide expression of IGF-I and IGFBP-2 in the MRL/lpr mouse. Using in situ hybridization and immunocytochemistry techniques, the expression of IGF-I and IGFBP-2 in MRL/lpr mouse was examined and compared to their congenic normal MRL-++ mouse counterparts from nine to 24 weeks of age. In the MRL-++ and MRL/lpr mouse kidneys, IGF-I and IGFBP-2 mRNA expression was limited to the cortical and medullary collecting ducts, while their immunoreactivity (IR) was localized to the cortical and medullary collecting ducts, loop of Henle, glomeruli and proximal tubules. Over time, and with progression of disease, the MRL/lpr mice displayed a significant increase in IGF-I IR and a modest increase in IGFBP-2 IR within the outer cortical glomeruli, which was associated with a significant increase in glomerulosclerosis and glomerular cell proliferation and with a significant decrease in renal function. In conclusion, this overexpression of IGF-I and IGFBP-2 within the glomeruli of the MRL/lpr mouse kidney supports their potential role in the alterations in renal function and morphology that accompany lupus nephritis.

Fetal rhesus monkey model of obstructive renal dysplasia.

BACKGROUND: Disorders of kidney development represent a major cause of renal failure and end-stage renal disease in the pediatric population. To understand further the prenatal pathogenesis of obstructive renal dysplasia, a fetal monkey model was developed using ultrasound-guided techniques. METHODS: Ureteropelvic obstruction (N = 13) was induced during the early or late second trimester by the injection of purified guluronic alginate spheres. All fetuses were monitored sonographically, and then fetal tissues were removed at varying time points during the second and third trimesters. RESULTS: There was no evidence of oligohydramnios during the course of gestation, and the obstructed kidneys were typically progressively smaller than the contralateral (nonobstructed) kidneys when monitored sonographically over time. Obstructed kidneys displayed most features of renal dysplasia, including numerous cortical cysts of various sizes derived predominantly from collecting ducts and glomeruli. Mesenchymal changes included expansion of both the cortical and medullary interstitium, as well as mesenchymal-myocyte transformation, expressed as pericystic and peritubular fibromuscular collar formation. An important feature of this model was the disruption of normal glomerular development and architecture, associated with significant podocyte apoptosis, evident as early as the prevascularized S-shaped nephron. As in other models, collecting duct cell apoptosis was apparent, particularly in areas of cyst formation and cellular atrophy. CONCLUSIONS: These results demonstrate the importance of this nonhuman primate model for exploring the pathophysiology of congenital obstructive uropathy and highlight the potential role of podocyte injury in determining long-term renal function associated with this condition.

Single-nucleotide polymorphisms of the proprotein convertase subtilisin/ kexin type 5 (PCSK5) gene.

The proprotein convertase. subtilisin/kexin type 5, or PCSK5, mediates post-translational endoproteolytic processing for several integrin alpha subunits. We identified two silent single-nucleotide polymorphisms (SNPs) in PCSK5, which were found to vary in frequency across ethnic groups. The identification of these amplification primers and SNPs provides tools to investigate PCSK5 for association with inflammatory or vascular phenotypes.

Expression of complement regulatory proteins in the developing human kidney.

Complement homologous restriction factor CD59 and complement receptor CD35 are typically involved in the regulation of the host defense system. Recent observations in the human fetal kidney suggest a further role for complement cell surface regulators CD35 and CD59 in kidney development and maturation. We investigated this possible role by localizing CD35 and CD59 protein and mRNA in the developing and adult kidney. Adult tissue and fetal tissue ontogeny were analyzed using immunohistochemistry and in situ hybridization. CD35 protein and mRNA were localized to the podocyte of the glomerulus in the human fetal and adult kidney. Expression was initiated after vascularization of the early developing glomerulus. CD59 protein and mRNA were observed as early as 8 weeks' gestation and were localized primarily to the ureteric duct epithelium in the fetal kidney and predominantly to the collecting duct in the adult. Interestingly, CD59 expression was translocated from the basolateral surface in the fetal kidney to the apical surface in the adult kidney. The specific spatial and temporal expression of CD35 and CD59 suggests a possible role for these complement regulatory proteins in renal cell differentiation.

Partial prevention of monocyte and granulocyte activation in experimental vein grafts by using a biomechanical engineering approach.

Leukocytes interact with endothelial cells and contribute to the development of vascular diseases such as thrombosis and atherosclerosis. These processes are possibly influenced by mechanical factors. This study focused on the role of mechanical stretch in the activation of monocytes and granulocytes in experimental vein grafts. Two models were created by using rats: a nonengineered vein graft with increased tensile stress, which was created by grafting a jugular vein into the abdominal aorta, and an engineered vein graft with reduced tensile stress, which was created by restricting the vein graft into a cylindrical sheath constructed by using fixative-treated intestinal tissue. The density of activated monocytes and granulocytes, which attached to the endothelium, and the distribution of the intercellular adhesion molecule (ICAM)-1 in endothelial cells were examined using immunohistological assays. It was found that, in nonengineered vein grafts, the density of activated monocytes and granulocytes increased significantly compared to that in normal jugular veins at day 1, 5, 10 and 20. At each observation time, the cell density in the proximal region of the nonengineered vein grafts was significantly higher than that in the middle and distal regions, and the cell density in the distal region was significantly higher than that in the middle region. These changes were associated with ICAM-1 clustering at day 1 and 5 and focal ICAM-1 un-regulation at day 10 and 20. In engineered vein grafts, the density of activated monocytes and granulocytes decreased significantly compared to that in nonengineered vein grafts at all observation times, although it was significantly higher than that in normal jugular veins. At each observation time, the cell density in the proximal and distal regions was significantly higher than that in the middle region, but no significant difference was found between the proximal and distal regions. ICAM-1 clustering along endothelial cell borders was found at day 1 and 5, but no apparent focal ICAM-1 up-regulation was found at day 10 and 20. These results suggested that mechanical stretch due to exposure to increased tensile stress contributed to the activation of monocytes and granulocytes in experimental vein grafts, and this event could be partially prevented by reducing tensile stress using a biomechanical engineering approach.

Flexor tendon repair using a stainless steel external splint. Biomechanical study on human cadaver flexor tendons.

A stainless steel external tendon splint was used in repair of cadaver tendons and compared with standard tendon repairs with suture. The splint was combined with a Kessler repair and tested against the Kessler, Becker, and Savage repairs in fresh human cadaver flexor digitorum profundus tendons. Biomechanical testing was done on a tensile testing machine, and load-displacement curves were generated. The repairs using the external tendon splint demonstrated a range of improvement of 32 to 146% in mean maximal tensile strength and a 20 to 185% improvement of mean ultimate tensile strength compared with all other repairs. The external tendon splint is relatively easy to apply to a tendon. The repair is strengthened and becomes capable of withstanding early active range of motion exercises. In vivo testing will be needed to assess the potential clinical usefulness of such a device.

Children on hunger strike: child abuse or legitimate protest?

The issue of children on hunger strike (voluntary total fasting) has not been reported before. The World Medical Association Declaration of Tokyo 1975 and the Declaration of Malta 1991 (revised 1992) provide clinicians with guidelines for the management of adult patients on hunger strike but do not mention children. We report the management of 14 Vietnamese children, aged 1 to 12 years, who took part in a hunger strike at a refugee detention centre in Hong Kong.

Current concepts in asthma management.

This short paper investigates the effects of prophylaxis on re-admission rates at the Royal Alexandra Hospital for Children, Camperdown, New South Wales.

Comparative studies of CDP-diacylglycerol synthase in rat liver mitochondria and microsomes.

CDP-diacylglycerol for polyglycerophosphatide biogenesis can be synthesized within rat liver mitochondria. Contamination by microsomal membranes cannot account for the CDP-diacylglycerol synthesis found in the mitochondria. Phosphatidic acid from egg lecithin was the best substrate for the synthesis of CDP-diacylglycerol in both subcellular fractions. Concentration curves for CTP and Mg2+ differed for the two subcellular fractions. Microsomal CDP-diacylglycerol synthase was specifically stimulated by the nucleotide GTP; this stimulatory effect by GTP was not observed in the mitochondrial fraction. By comparison, the microsomal enzyme was more sensitive towards sulfhydryl inhibitors than the mitochondrial enzyme. The enzymes could be solubilized from the membrane fractions using 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate, and the detergent-soluble activity could be partially restored by addition of phospholipids. Based on the differences in properties, it was concluded that there are two distinct enzyme localizations for CDP-diacylglycerol synthesis in mitochondria and microsomes from rat liver.

CDP-diacylglycerol synthesis in rat liver mitochondria.

CDP-diacylglycerol for polyglycerophosphatide biogenesis can be synthesized within rat liver mitochondria. This membrane-associated enzyme was predominantly located in the inner mitochondrial membrane. GTP had a significant effect in activating the microsomal CDP-diacylglycerol synthase, especially if the microsomes were preincubated with GTP in the presence of phosphatidic acid. This stimulatory effect of GTP on the microsomal enzyme was not detected in the mitochondrial fractions. The enzymes could be solubilized from the membrane fractions using CHAPS, and the detergent-soluble activity partially restored by addition of phospholipids. Mitochondrial and microsomal CDP-diacylglycerol synthase activity could be completely separated by anion-exchange column chromatography. The mitochondrial and microsomal CDP-diacylglycerol synthases appear to be two distinct enzymes with different localization and regulatory characteristics.

Biosynthesis of phosphatidic acid by glycerophosphate acyltransferases in rat liver mitochondria and microsomes.

The acyltransferases that catalyze the synthesis of phosphatidic acid from labelled sn-[14C]glycero-3-phosphate and fatty acyl carnitine or coenzyme A derivatives have been shown to be present in both isolated mitochondria and microsomes from rat liver. The major reaction product was phosphatidic acid in both subcellular fractions. A small quantity of lysophosphatidic acid and neutral lipids were produced as by-products. Divalent cations had significant effects on both mitochondrial and microsomal fractions in stimulating acylation using palmitoyl CoA, but not when palmitoyl carnitine was used as the acyl donor. Palmitoyl CoA and palmitoyl carnitine could be used for acylation by both mitochondria and microsomes. Mitochondria were more permeable to palmitoyl carnitine and readily used it as the substrate for acylation. On the other hand, microsomes yielded a better rate with palmitoyl CoA and the rate of acylation from palmitoyl carnitine in microsomes was correlated with the degree of mitochondrial contamination. The enzymes were partially purified from Triton X-100 extracts of subcellular fractions. Based on the differences of substrate utilization, products formed, divalent cation effects, molecular weights, and polarity, the mitochondrial and microsomal acyltransferases appeared to be different enzymes.

Examination of the potential role of the glycerophosphorylcholine (GPC) pathway in the biosynthesis of phosphatidylcholine by liver and lung.

The potential involvement of the glycerophosphorylcholine (GPC) pathway for the synthesis of phosphatidylcholine (PC) has been examined in rat liver and lung and in a human line, the A549 cell which possesses characteristics representative of mature alveolar type II epithelial cells. Although mitochondrial and microsomal fractions from the above sources readily incorporated radioactive glycerophosphate into lipids, the only incorporation observed with radioactive GPC was a small variable labelling with the mitochondrial and microsomal fractions from rat lung. Even with these fractions, no radioactivity from GPC was incorporated into PC or lysoPC. Attempts to increase the incorporation of GPC into lipids by manipulating the incubation conditions were unsuccessful. It was concluded that the occurrence of the GPC pathway in liver and lung is unlikely.