PUF60-related developmental disorder: A case series and phenotypic analysis of 10 additional patients with monoallelic PUF60 variants.

PUF60-related developmental disorder (also referred to as Verheij syndrome), resulting from haploinsufficiency of PUF60, is associated with multiple congenital anomalies affecting a wide range of body systems. These anomalies include ophthalmic coloboma, and congenital anomalies of the heart, kidney, and musculoskeletal system. Behavioral and intellectual difficulties are also observed. While less common than other features associated with PUF60-related developmental disorder, for instance hearing impairment and short stature, identification of specific anomalies such as ophthalmic coloboma can aid with diagnostic identification given the limited spectrum of genes linked with this feature. We describe 10 patients with PUF60 gene variants, bringing the total number reported in the literature, to varying levels of details, to 56 patients. Patients were recruited both via locally based exome sequencing from international sites and from the DDD study in the United Kingdom. Eight of the variants reported were novel PUF60 variants. The addition of a further patient with a reported c449-457del variant to the existing literature highlights this as a recurrent variant. One variant was inherited from an affected parent. This is the first example in the literature of an inherited variant resulting in PUF60-related developmental disorder. Two patients (20%) were reported to have a renal anomaly consistent with 22% of cases in previously reported literature. Two patients received specialist endocrine treatment. More commonly observed were clinical features such as: cardiac anomalies (40%), ocular abnormalities (70%), intellectual disability (60%), and skeletal abnormalities (80%). Facial features did not demonstrate a recognizable gestalt. Of note, but remaining of unclear causality, we describe a single pediatric patient with pineoblastoma. We recommend that stature and pubertal progress should be monitored in PUF60-related developmental disorder with a low threshold for endocrine investigations as hormone therapy may be indicated. Our study reports an inherited case with PUF60-related developmental disorder which has important genetic counseling implications for families.

Exposure risk and COVID-19 infection among frontline health-care workers: A single tertiary care centre experience.

BACKGROUND: There is limited data on frontline health-care workers and risk of COVID-19 from the developing nations. It is imperative to identify those at higher risk to prevent further transmission. We assessed the relationship between exposure risk and COVID-19 among front-line health-care workers who were primary contacts of a COVID-19 patient. METHODS: A retrospective cohort study was conducted among front-line health-care workers in a tertiary care hospital who were exposed to a COVID-19 patient. Information on demographic factors, medical history, exposure related factors and subsequently COVID-19 lab reports were collected. An exposure risk assessment designed collating various exposure related factors categorized the participants into those with high and low risk. We used logistic regression to estimate the odds ratio of our primary outcome, a positive COVID-19 test when the independent variables were exposure risk, age, gender and occupation. RESULTS: Among1858 frontline workers who were primary contacts of a COVID-19 patient at the hospital, 106 (5.7%) incident reports of a positive COVID-19 test were recorded. None of the exposure related factors had any significant association with a positive COVID-19 test. However, high exposure risk category was significantly associated with COVID-19 positive test at the end of quarantine. CONCLUSION: COVID-19 was more frequent among front-line health-care workers who belonged to high exposure category. Education at different levels of service delivery at hospitals is required for best practice in order to prevent COVID-19 among health care providers. There is need to develop additional strategies to ensure that the information is translated in to practice.

POWIFF- Prospective study of wrist internal fixation of fracture: A protocol for a single centre, superiority, randomised controlled trial to study the efficacy of the VRP (2.0) distal radius plate (Austofix) versus the VA-LCP (Depuy-Synthes) for distal radius fractures.

BACKGROUND: Distal radial fractures are one of the most common orthopaedic cases that present to the A&E department. Surgical intervention is warranted in displaced intraarticular fractures and fractures with more than the recommended angulation or shortening, and is most commonly treated with volarly placed fixed angle locking plates. The aim of this study is to determine and compare the efficacy of two different plates for surgical treatment of distal radius fractures. The VRP 2.0 is a new plate produced by the Austofix company and this system will be compared against the VA-LP (Variable angle-locking plate) produced by Depuy-Synthes which has been used as the standard treatment device. METHODS AND DESIGN: Patients between the ages of 18 and 80 presenting to the Royal Adelaide Hospital with isolated closed distal radial fractures will be invited to participate in this study. A total of 200 patients are required to provide 90% statistical power at a 5% alpha level to detect a difference of 11.5 points on the PRWE (Patient rated Wrist evaluation) score. The primary outcome measure will be the PRWE score while the secondary outcome measures will include the DASH score, EQ5D score, clinical range of movements, grip strength as well as patient perceived return of function at the wrist and time to resumption to work. These will be measured at 6 weeks, 3 months and 12 months. Radiographic indices including the radial tilt, length, volar inclination and plate prominence will also be measured. Complications will be recorded up to 12 months. Post hoc comparisons will be done using paired t tests. An intention to treat and a per protocol analysis will be done to compare the 2 groups. DISCUSSION: Distal radial fractures are increasingly being treated by internal fixation using volar locking plates. However, there is no prospective study to date comparing one plate against another in terms of outcome and complications. This study could provide more information about the best way to treat these injuries surgically. TRIAL REGISTRATION: The trial is registered with the Australia New Zealand Clinical Trials Registry (ANZCTR). Trial registration date-17/11/2016. Trial registration number- ACTRN12616001590459 .

Physical restraint: perceptions of nurse managers, registered nurses and healthcare assistants.

AIM: To examine the perceptions of nurse managers, registered nurses and healthcare assistants of physical restraint use on older people in a long-term care setting in the Republic of Ireland. BACKGROUND: The use of physical restraint, although controversial, persists in long-term care settings, despite recommendations for restraint-free environments. Perception and attitude of staff can influence use of physical restraint. METHODS: A descriptive cross-sectional design was used. A total of 250 nursing and healthcare assistant staff were recruited. A questionnaire incorporating demographics and the Perceptions of Restraint Use Questionnaire was used. Descriptive and inferential statistical analyses were conducted. RESULTS: Mean age of respondents (n = 156) was 41 years, and the majority were female. Overall, a low level of importance was attached to the use of restraint. Nurse managers and registered nurses compared favourably with healthcare assistants who attached a higher importance to use of restraint. Across all three staff groups, greatest importance was attached to the use of physical restraint for reducing falls, followed by prevention of treatment interference. Restraint was least favoured as a means of impairment management. Education was not an explanatory factor in perceived importance of physical restraint use. CONCLUSION: Nurse managers and registered nurses are unlikely to use physical restraint. However, there is concern regarding perception of healthcare assistants on use of restraint. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Results from this study compare favourably with those in countries that have no policy on physical restraint use. Educational programmes alone are insufficient to address use of physical restraint. Attention to skill mix with adequate support for healthcare assistants in long-term care settings is recommended.

Contemporary acetabular fracture surgery: treading water or swimming upstream?

In the time since Letournel popularised the surgical treatment of acetabular fractures, more than 25 years ago, there have been many changes within the field, related to patients, surgical technique, implants and post-operative care. However, the long-term outcomes appear largely unchanged. Does this represent stasis or have the advances been mitigated by other negative factors? In this article we have attempted to document the recent changes within the surgery of patients with a fracture involving the acetabulum, outline contemporary management, and identify the major problem areas where further research is most needed. Cite this article: Bone Joint J 2017;99-B:1125-31.

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

Astaxanthin modulates osteopontin and transforming growth factor ß1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration.

OBJECTIVES: To evaluate the effect of astaxanthin on renal angiotensin-I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor ß1 (TGF-ß1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model. To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones. MATERIALS AND METHODS: The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF-ß1 levels. Renal ACE levels were quantified by an enzyme-linked immunosorbent assay method. Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)-energy-dispersive X-ray (EDX). RESULTS: The renal ACE levels and the expression of OPN and TGF-ß1 were upregulated in the nephrolithiasis-induced rats. Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF-ß1. SEM-EDX analysis showed that crystal deposition was reduced in the astaxanthin-treated nephrolithiatic group. Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF-ß1 expressions. CONCLUSIONS: Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin-angiotensin system (RAS), which reduced the expression of OPN and TGF-ß1 levels. Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down-regulating the expression of OPN and TGF-ß1.

Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.

Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.

The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment.

FOXM1 is implicated in genotoxic drug resistance but its role and mechanism of action remain unclear. Here, we establish that γH2AX foci, indicative of DNA double-strand breaks (DSBs), accumulate in a time-dependent manner in the drug-sensitive MCF-7 cells but not in the resistant counterparts in response to epirubicin. We find that FOXM1 expression is associated with epirubicin sensitivity and DSB repair. Ectopic expression of FOXM1 can increase cell viability and abrogate DSBs sustained by MCF-7 cells following epirubicin, owing to an enhancement in repair efficiency. Conversely, alkaline comet and γH2AX foci formation assays show that Foxm1-null cells are hypersensitive to DNA damage, epirubicin and γ-irradiation. Furthermore, we find that FOXM1 is required for DNA repair by homologous recombination (HR) but not non-homologous end joining (NHEJ), using HeLa cell lines harbouring an integrated direct repeat green fluorescent protein reporter for DSB repair. We also identify BRIP1 as a direct transcription target of FOXM1 by promoter analysis and chromatin-immunoprecipitation assay. In agreement, depletion of FOXM1 expression by small interfering RNA downregulates BRIP1 expression at the protein and mRNA levels in MCF-7 and the epirubicin-resistant MCF-7 Epi(R) cells. Remarkably, the requirement for FOXM1 for DSB repair can be circumvented by reintroduction of BRIP1, suggesting that BRIP1 is an important target of FOXM1 in DSB repair. Indeed, like FOXM1, BRIP1 is needed for HR. These data suggest that FOXM1 regulates BRIP1 expression to modulate epirubicin-induced DNA damage repair and drug resistance.

Evaluation of the sensitivity of a digital plaque imaging system on different tooth surfaces.

OBJECTIVE: The study aimed to test the sensitivity of digital plaque imaging in distinguishing the effectiveness of test and control mouthwashes for different groups of tooth surfaces. METHODS: The study was a double-blind, parallel, randomized, controlled clinical trial. Sixty subjects underwent scaling and polishing after recruitment, and attended their baseline examination after a washout phase of a minimum of seven days. They were then randomly assigned to one of two mouthwashes: 1) 0.05% CPC mouthwash; and 2) matching placebo mouthwash without CPC. Both groups were asked to use their assigned mouthwash and to refrain from any other oral hygiene measures for a period of eight days. At the baseline and day 8 visits, digital images of tooth surfaces were captured using Quantitative Light-induced Fluorescence (QLF) imaging, and plaque area as a percentage of the tooth surface was measured. Comparisons were carried out between the products for different groups of tooth surfaces. The data generated by the software were validated by a manual plaque outlining technique. RESULTS: Fifty-eight (58) subjects completed the study. More plaque was detected on the facial surfaces for the whole mouth (42.88% coverage for CPC and 46.45% for placebo) than the whole mouth lingual surfaces (7.23% coverage for CPC and 11.10% for placebo). Significant differences were observed between the products for the following areas: all tooth surfaces (p = 0.032), anterior lingual (p = 0.005), posterior lingual (p = 0.003), and whole mouth lingual (p = 0.001), whereas there were no differences between the products for anterior facial, anterior (facial & lingual), posterior facial, posterior (facial & lingual), and whole mouth facial. A strong correlation (R = 0.793, p < 0.001) was observed between the data (mean difference of percentage plaque coverage) generated by the analyzing program and that from the manual plaque outlining technique. CONCLUSION: The digital plaque imaging system was able to distinguish between the products when looking at the whole mouth. Digital imaging was better able to separate the groups when examining the lingual surfaces than facial.

Sebaceous differentiation in odontogenic keratocyst.

Sebaceous glands are common in the oral mucosa, but are not normally present with in the jaws. A case of an odontogenic keratocyst with sebaceous glands in the epithelium in a 12-year-old child is presented here, with special emphasis on its histogenesis.

Clear cell ameloblastoma in a young child--an enigma in diagnosis.

Clear cell ameloblastoma is an odontogenic tumour with aggressive behaviour usually noticed in 6th decade of life. It is histologically characterized by an ameloblastomatous component intermixed with an extensive clear cell component. Here is a case report of an unusual occurrence in a 5-year-old child. The rarity of this tumour and young age of the patient are some of the rare features, which need documentation. The importance of its diagnosis and various differential diagnoses are discussed.

Oral pemphigus vulgaris: clinicopathologic study of 20 cases.

Pemphigus vulgaris (PV) is a vesiculobullous lesion that produces intraepithelial blisters in skin and mucous membrane. The oral mucosa is often the first site to be affected by the disease. Although oral PVis a well characterized condition, the detailed clinical and histopathological study in Malabar population has not been reported. A clinicopathologic study of 20 cases of oral PV observed over a span of 2 years from January 2004 to January 2006 is reported. For these 20 cases, the mean age was 42.3 years and male:female ratio was 2:3. The most commonly affected sites were the buccal mucosa and palate. Histopathologic examination with direct immunofluorescence was the method of diagnosis in all cases. Suprabasilar clefting with acantholytic cells can be seen histopathologically and IgG positivity in direct immunofluorescence in all cases that have been studied.

Molecular characterization of bovine group A rotavirus G3P[3] strains.

During a surveillance study, four of 130 group A rotavirus strains, detected from diarrheic calves in Eastern India, exhibited G3P[3] specificities. Molecular characterization of VP7 and VP8(*) genes of one such strain [named as RUBV3 (RU: ruminant and BV: bovine)] revealed genetic relatedness to a G3P[3] simian strain, RRV, and RRV-related caprine strain GRV. Strain RUBV3 had VP6, NSP4 and NSP5 genes of bovine origin. Therefore, the present study provides evidence for multiple reassortment events involving ruminant and simian strains and, to our knowledge, is the first report of detection of bovine group A rotavirus strains with G3P[3] specificities.

Evidence for interstate transmission and increase in prevalence of bovine group B rotavirus strains with a novel VP7 genotype among diarrhoeic calves in Eastern and Northern states of India.

During a surveillance study (2003-2005) in a cattle market in Kolkata city, state of West Bengal, Eastern India, 34 (13.0%) of 260 calves with diarrhoea were positive for group B rotaviruses (GBR) by RNA electrophoresis in polyacrylamide gels. Analysis of the partial VP7 gene sequence of 28 of the 34 GBR strains revealed maximum identities (97.7-99.5% at nucleotide level and 97.8-100% at amino-acid level) with the novel bovine GBR 'Kolkata strains' reported in an earlier surveillance study (1.5%, n=192, 2001-2002) from the same cattle market, and shared low identities of 73.7-78.9% and 80.8-89.6%; 62.6-66.2% and 59.8-65.4%; 58.9-62.2% and 48.6-54.9% at nucleotide and amino-acid level with other bovine, human, and murine GBR. The GBR-infected calves were traced to districts in neighbouring states of West Bengal. Therefore, the present study reports a rapid increase in prevalence (13.0% in 2003-2005 against 1.5% in 2001-2002) of novel GBR strains among calves with diarrhoea, and provides evidence for interstate transmission of GBR.