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This paper describes a preliminary cross-sectional study which aimed to compare levels of death anxiety and coping responses in palliative care and accident and emergency (A & E) nurses. Forty-three nurses (23 from palliative care and 20 from A & E) were recruited from a district general hospital and nearby hospice. Both sites had the same mean annual death rate of 150 patients. Death anxiety was measured by the Death Attitude Profile-Revised Questionnaire and coping responses were elicited by a semi-structured interview. As hypothesized, hospice nurses had lower death anxiety and they were more likely to recall both good and difficult experiences related to patient care. Unlike the hospice nurses, a subgroup (20%) of A & E nurses reported that they were unable to discuss problems with colleagues. The study has implications for the development of institutional support for staff to enable nurses to provide good quality care for dying patients and bereaved people. [ABSTRACT FROM AUTHOR]

ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants). In this study, we describe the clinical features of 13 additional individuals and review the data on a total of 27 individuals (16 individuals with monoallelic and 11 with biallelic ANK3 variants) and demonstrate that the phenotype for biallelic variants is more severe. The phenotypic features include language delay (92%), autism spectrum disorder (76%), intellectual disability (78%), hypotonia (65%), motor delay (68%), attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) (57%), sleep disturbances (50%), aggressivity/self-injury (37.5%), and epilepsy (35%). A notable phenotypic difference was presence of ataxia in three individuals with biallelic variants, but in none of the individuals with monoallelic variants. While the majority of the monoallelic variants are predicted to result in a truncated protein, biallelic variants are almost exclusively missense. Moreover, mono- and biallelic variants appear to be localized differently across the three different ankyrin-G isoforms, suggesting isoform-specific pathological mechanisms., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Purpose: Multiple studies suggest an association between DLG2 and neurodevelopmental disorders and indicate the haploinsufficiency of this gene; however, few cases have been thoroughly described. We performed additional studies to confirm this clinical association and DLG2 haploinsufficiency., Methods: Chromosomal microarray analysis was performed on 11,107 patients at the Cytogenetics Laboratory at the University of Alabama at Birmingham. The Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database were selected for the association analysis. Fifty-nine patients from the literature and DECIPHER, all having DLG2 intragenic deletions, were included for comprehensive analysis of the distribution of these deletions., Results: A total of 13 patients with DLG2 intragenic deletions, from 10 families in our cohort, were identified. Nine of 10 probands presented with clinical features of neurodevelopmental disorders. Congenital anomalies and dysmorphism were common in our cohort of patients. Association analysis showed that the frequency of DLG2 deletions in our cohort is significantly higher than those in the Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database. Most of DLG2 intragenic deletions identified in 69 unrelated patients from our cohort, the literature, and DECIPHER map to the 5' region of the gene, with a hotspot centered around HPin7, exon 8, and HPin8., Conclusion: Our findings reinforce the link between DLG2 intragenic deletions and neurodevelopmental disorders, strongly support the haploinsufficiency of this gene, and indicate that these deletions might also have an association with congenital anomalies and dysmorphism., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

There have been multiple reports of eye infections caused by antibiotic-resistant bacteria, with increasing evidence of ineffective treatment outcomes from existing therapies. With respect to corneal infections, the most commonly used antibiotics (fluoroquinolones, aminoglycosides, and cephalosporines) are demonstrating reduced efficacy against bacterial keratitis isolates. While traditional methods are losing efficacy, several novel technologies are under investigation, including light-based anti-infective technology with or without chemical substrates, phage therapy, and probiotics. Many of these methods show non-selective antimicrobial activity with potential development as broad-spectrum antimicrobial agents. Multiple preclinical studies and a limited number of clinical case studies have confirmed the efficacy of some of these novel methods. However, given the rapid evolution of corneal infections, their treatment requires rapid institution to limit the impact on vision and prevent complications such as scarring and corneal perforation. Given their rapid effects on microbial viability, light-based technologies seem particularly promising in this regard.

Inguinal hernias are rare in female infants, and when present, there is an increased incidence of androgen insensitivity in these infants. We present a case of bilateral inguinal hernias in a 26-day-old full-term phenotypic female. On physical exam, the patient was found to have bilateral palpable inguinal masses which were suspected to be testicular tissue on ultrasound. Patient also had bilateral inguinal hernias, but otherwise there were no other concerning symptoms, and the remaining physical examination was overall unremarkable. Initial workup included a pelvic ultrasound that did not visualize a uterus or ovaries. In addition, genetic testing confirmed normal male genotype with 100% 46, on fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (CGH) was negative and did not reveal any copy number changes. Molecular testing was consistent with a diagnosis of androgen insensitivity syndrome with hemizygous pathogenic variant in the androgen receptor (AR) gene (deletion of Exon 2 of AR gene Xq12 ). This case highlights the importance of a high clinical suspicion of complete androgen insensitivity syndrome (CAIS) in a phenotypic female infant with inguinal hernias. To our knowledge, this is one of the earliest diagnoses of CAIS in a phenotypically female infant.

Purpose: To explore blinking patterns and sagittal eyelid misalignment in the East Asian eye., Methods: Forty-four participants (22 females; age 26 ± 5 years; 52% of East Asian ethnicity) were enrolled in this pilot study and subdivided, based on upper eyelid crease presence and extent, into single (n = 10), partial (n = 11) or double (n = 23) eyelid crease groups. Blinking was filmed surreptitiously with high-speed video simultaneously from an inferior temporal and frontal view. Spontaneous blink rate and type (incomplete, almost complete, or complete) were assessed over a 30 s period. Sagittal misalignment of the lids on closure was graded during complete spontaneous blinks, voluntary lid closure and voluntary maximal lid contraction (squeezing). A 0.15 µL drop of lissamine green was placed on the central lower lid margin and the number and type of blinks required to eliminate the drop informed complete palpebral apposition during blinking., Results: Mean ± SD blink rates averaged 16.9 ± 10.5 blinks/minute. The proportion of incomplete blinks was 83 ± 22% in single, 58 ± 35% in partial and 59 ± 30% in double eyelid crease groups. The sagittal misalignment of the lid margins during blinking was limited to approximately one-third of the lid margin width; this was similar for all lid morphologies and blink types. The lissamine green drop was eliminated only by voluntary maximal lid contraction, and was similar in all groups (p = 0.97)., Conclusions: Incomplete blinking and sagittal lid misalignment of the central eyelid margin predominate in habitual blinking, irrespective of lid morphology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Preclinical evaluation of the therapeutic potential of antimicrobial 265 nm UVC for infectious keratitis., Methods: Four experiments explored UVC: 1) impact on bacterial and fungal lawns on agar, in individual or mixed culture, 2) bacterial inactivation dose in an in vitro deep corneal infection model, 3) dose validation in an ex vivo porcine keratitis model and 4) efficacy in a masked, randomised, controlled murine keratitis trial using bioluminescent Pseudomonas aeruginosa., Results: Minimum effective UVC exposures ranged between 2 s and 5 s for lawn bacteria and fungi in individual or mixed culture. Significant P. aeruginosa growth inhibition in the in vitro infection model was achieved with 15 s UVC, that resulted in a >3.5 log 10 reduction of bacteria in a subsequent ex vivo keratitis model (p < 0.05). Bioluminescence fell below baseline levels in all treated animals, within 8 h of treatment (p < 0.05), in the in vivo study. Re-epithelialisation with corneal clarity occurred within 24 h in 75% of UVC-treated cases, with no relapse at 48 h. On plating, bacteria were recovered only from untreated controls., Conclusions: UVC inhibited all tested bacteria and fungi, including mixed culture and strains linked to antibiotic resistance, in vitro, with exposures of ≤ 5 s. In vitro and ex vivo testing confirmed therapeutic potential of 15 s UVC. In vivo, 15 s UVC administered in two doses, 4 h apart, proved effective in treating murine bacterial keratitis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, inherited in an X-linked manner. Males are severely affected. Female phenotypes vary from asymptomatic to severe, and symptoms may be triggered by high metabolic states like childbirth. Literature on OTC deficiency in pregnancy and placental pathology is limited., Methods: Pathology records were searched at a single referral center from 2000-2020 and identified three placental cases from two mothers heterozygous for OTC deficiency. Placental pathology and maternal and neonatal history were reviewed in detail., Results: The placenta from one symptomatic mother carrying an affected male fetus showed widespread high-grade fetal vascular malperfusion (FVM) lesions of varying age. These lesions were not seen in the two placentas from the asymptomatic mother., Discussion: In cases of symptomatic maternal OTC deficiency, our findings highlight the need for placental examination. Since thrombotic events in the placenta have the potential to associate with fetal and neonatal endothelial damage, a high index of suspicion for neonatal thrombosis may be warranted.

Abstract: Repeated presentations of a rare symptom in a patient should make a physician stop and evaluate for rare conditions. This is a report of a teenager with multiple episodes of rhabdomyolysis and weakness. He was eventually diagnosed as having McArdle muscular dystrophy, or glycogen storage disease type V. His rhabdomyolysis has been severe, with a creatinine kinase level of >320,000 U/L, myoglobinuria, transaminitis, and elevated bilirubin. He has a low threshold for triggering rhabdomyolysis, such as doing an hour of aerobic exercise 2 days in a row. McArdle disease is a glycogen storage disorder in which the skeletal muscle cannot convert glycogen to glucose. Unlike other glycogen storage disorders, McArdle muscular dystrophy only affects the skeletal muscle, sparing the brain and visceral organs, leading to a vague phenotype. These patients have exercise intolerance, muscle cramps, and rhabdomyolysis. Many patients report loading with simple carbohydrates before exercise, as they have learned that this can increase their stamina. The vague symptoms can lead to decades of delay in diagnosis and significant mismanagement. Rhabdomyolysis is the most dangerous sign of McArdle disease, and it can lead to acute kidney injury, resulting in renal failure requiring dialysis in the severest cases.Rhabdomyolysis has numerous causes, but when it is recurrent, especially with seemingly insignificant triggers, one needs to develop a broader differential and pursue advanced testing. This testing can include specific exercise tests, genetic sequencing, and muscle biopsy. This case report will guide the clinician through the process of evaluating recurrent rhabdomyolysis, working through the differential diagnosis and testing options.1., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Few studies have evaluated corneal crosslinking (CXL) in a prospective, randomised fashion. This study aimed to determine the efficacy and safety of CXL to reduce the progression of keratoconus., Methods: Prospective, unmasked, randomised, contralateral eye controlled trial at a tertiary eye centre., Participants: Individuals with bilateral progressive keratoconus. One eye from each subject was randomised to CXL and the contralateral, untreated eye acted as the control., Primary Outcome Measure: change in maximum keratometry., Secondary Outcome Measures: uncorrected distance visual acuity, spectacle corrected distance visual acuity, spherical equivalent refraction, simulated keratometry, corneal astigmatism, minimum pachymetry and complications., Results: Thirty-eight individuals (mean age 21.1 ± 6.7 years) were enrolled with one eye treated with CXL. At 5 years, there was a mean decrease in maximum keratometry of treated eyes (-1.45 ± 2.25 D) compared to an increase among the controls (1.71 ± 2.46 D; p < 0.001). There were significant differences between the treated and control groups in the mean change of Steep SimK (-1.07 ± 1.22 vs. 0.96 ± 1.97 D; p < 0.001), Flat SimK (-0.61 ± 1.34 vs. 0.43 ± 1.12 D; p < 0.001), corneal astigmatism (-0.45 ± 1.31 vs. 0.63 ± 1.52 D; p < 0.01) and minimum pachymetry (-32.49 ± 26.32 vs. -13.57 ± 24.11 μm; p < 0.01). Complications included sterile infiltrates (n = 2), microbial keratitis (n = 1), persistent corneal haze/scarring at 5 years (n = 4) and loss of ≥2 lines of corrected distance visual acuity (n = 3)., Conclusions: CXL is an effective and relatively safe intervention to halt or reduce the progression of keratoconus in the majority of eyes for at least 5 years., (© 2021 Royal Australian and New Zealand College of Ophthalmologists.)

Background: Ultraviolet (UV) light is naturally antimicrobial, but risks associated with UV overexposure have limited its clinical application. This systematic review evaluates the safety and efficacy of UV light treatment of superficial human infections., Methods: MEDLINE, Embase, Cochrane CENTRAL, ANZCTR and US National Library of Medicine were searched (March 25, 2020). Clinical studies applying UV light (200-400 nm) for superficial infections and non-clinical studies evaluating the antimicrobial effects of UV light on human samples were included. Randomised controlled trials (RCTs) and non- RCTs were appraised using the Cochrane risk of bias and the ROBINS-I tools, respectively., Results: Eleven RCTs, seven non-RCTs, 24 case studies, and 11 in vitro studies were included. Most clinical studies (34/42) evaluated UVA treatment for microbial keratitis (MK) using cross-linking (UVA-CXL) methods. Six clinical studies assessed UVC; one, UVB; and one, broadband UV for chronic skin infections. Pooled data analysis showed no difference in the time to wound resolution with UVA-CXL relative to standard treatment (mean difference [MD]: -18.20 [95% CI: -39.04 to 2.65] days; p = 0.09). Adverse event incidence was similar to control for UVA-CXL in MK (RR: 0.70 [95%CI: 0.32-1.79]; 5 RCTs) and UVC in skin infections (RR: 0.63 [95%CI: 0.25-1.54]; 2 RCTs)., Conclusion: Alone or as an adjunct to standard therapy, UV light shows promise as a safe and effective treatment for a wide range of infections. Applications of UV light as an anti-infective agent are deserving of further evaluation, especially in the context of growing antibiotic resistance., Registration: PROSPERO registration number CRD42020176510., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates and has potential to treat corneal infection if safety can be confirmed., Method: Safety of 265 nm, 1.93 mW/cm 2 intensity UVC (15-300 s exposures) was investigated in vitro via cyclobutane pyrimidine dimer (CPD) formation in DNA of human cultured corneal epithelial cells; ex vivo, by evaluating UVC transmissibility as a function of porcine corneal thickness; and in vivo, by evaluating CPD induction in the mouse cornea following UVC exposure., Results: A single exposure of 15 s UVC did not induce significant CPD formation (0.92 ± 1.45%) in vitro relative to untreated control (p = 0.93) whereas 300 s exposure caused extensive CPD formation (86.8 ± 13.73%; p < 0.0001). Cumulative exposure to 15 s UVC daily for 3 days induced more CPD (14.6 ± 8.2%) than a single equivalent 45 s exposure (8.3 ± 4.0%) (p < 0.001) but levels returned to baseline within 72 h (p = 0.29), indicating highly efficient DNA repair. Ex vivo, UVC transmission decreased sharply with increasing corneal thickness, confirming UVC effects are limited to the superficial corneal layers. In vivo evaluations demonstrated no detectable CPD after three consecutive daily 15 s UVC exposures, whereas a single 300 s exposure induced extensive CPD formation in superficial corneal epithelium., Conclusion: Up to three daily doses of 15 s UVC, in vivo, appear safe with respect to CPD formation. Ongoing research exploring UVC as a possible treatment for microbial keratitis is warranted., (Copyright © 2021. Published by Elsevier Inc.)

A common feature among pre-malignant lesions is the induction of hypoxia through increased cell propagation and reduced access to blood flow. Hypoxia in breast cancer has been associated with poor patient prognosis, resistance to chemotherapy and increased metastasis. Although hypoxia has been correlated with factors associated with the latter stages of cancer progression, it is not well documented how hypoxia influences cells in the earliest stages of transformation. Using the immortalized MCF-10A breast epithelial cell line, we used hypoxic culture conditions to mimic reduced O2 levels found within early pre-malignant lesions and assessed various cellular parameters. In this non-transformed mammary cell line, O2 deprivation led to some changes not immediately associated with cancer progression, such as decreased proliferation, cell cycle arrest and increased apoptosis. In contrast, hypoxia did induce other changes more consistent with an increased metastatic potential. A rise in the CD44+CD24-/low-labeled cell sub-population along with increased colony forming capability indicated an expanded stem cell population. Hypoxia also induced cellular and molecular changes consistent with an epithelial-to-mesenchymal transition (EMT). Furthermore, these cells now exhibited increased migratory and invasive abilities. These results underscore the contribution of the hypoxic tumour microenvironment in cancer progression and dissemination.

Purpose of Review: The current review will focus on the current knowledge of the contribution of both germline and somatic mutations to the development and management of cancer in pediatric patients., Recent Findings: It has long been thought that genetic mutations in both germline and somatic cells can contribute to the development of cancer in pediatric patients. With the recent advances in genomic technologies, there are now over 500 known cancer predisposition genes. Recent studies have confirmed an 8.5-14% germline mutation rate in cancer predisposition genes in pediatric cancer patients., Summary: The discovery of both germline and somatic cells mutation(s) in pediatric cancer patients not only aids in the management of current disease, but can also have direct implications for future management as well as the medical management of family members.

Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laboratory records of 89 culture positive cases were retrospectively reviewed and antibiotic sensitivity patterns compared with previous studies from other NZ centres. Results. From 126 positive cultures, 35 species were identified. Staphylococcus was identified to be the most common isolate (38.2%), followed by Pseudomonas (21.3%). Over the last decade, infection due to Pseudomonas species, in the same setting, has increased (p ≤ 0.05). Aminoglycosides, cefazolin, ceftazidime, erythromycin, tetracycline, and doxycycline were 100% effective against tested isolates in vitro. Amoxicillin (41.6%), cefuroxime (33.3%), and chloramphenicol (94.7%) showed reduced efficacy against Gram-negative bacteria, whereas penicillin (51%) and ciprofloxacin (98.8%) showed reduced efficacy against Gram-positive bacteria. Conclusions. Despite a shift in the spectrum of bacterial keratitis isolates, antibiotic sensitivity patterns have generally remained stable and show comparability to results within the last decade from NZ centres.

The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.

Background: Blepharophimosis-ptosis-epicanthus inversus syndrome is an autosomal dominant condition because of mutations or deletions of the FOXL2 gene. Microcephaly is not associated with FOXL2 mutations but has been reported in individuals with chromosome 3q deletions, which include the FOXL2 gene and other contiguous genes. The ATR gene has been reported as a candidate gene for microcephaly in individuals with contiguous deletion of chromosome 3q involving the FOXL2 gene., Patient: We describe a girl with blepharophimosis-ptosis-epicanthus inversus syndrome along with acquired microcephaly and intellectual disability., Results: Our patient had a deletion of chromosome 3q22.2q23, which does not include the ATR gene but does include the PIK3CB gene as a candidate gene for microcephaly., Conclusion: We propose that the PIK3CB gene included in our patient's chromosome 3q deletion may be the gene responsible for microcephaly and other patients with blepharophimosis-ptosis-epicanthus inversus syndrome because of a chromosome 3q deletion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To investigate the association between PTEN loss and IGFBP2 expression in a series of triple-negative breast cancers and to relate this expression to basal cytokeratin expression and clinicopathologic features., Methods: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining., Results: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation (P = .026), cytokeratin 5/6 positivity (P = .028), and IGFBP2 expression (P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity (P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant., Conclusions: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression.

Identifying contact allergens in ophthalmic medications can be a challenging and daunting experience. We summarize data on topical ophthalmic medications with the potential to cause periorbital contact dermatitis and allergic conjunctivitis, highlighting current dilemmas and controversies in this area. The following groups of allergens are reviewed: preservatives, antiglaucoma medications (prostaglandin analogues, β-blockers, carbonic anhydrase inhibitors, parasympathomimetics, sympathomimetics), antiinflammatory medications (nonsteroidal antiinflammatory drugs, corticosteroids), antibiotics, antivirals, antiallergic medications (antihistamines, cromones), anaesthetics, mydriatics, and cycloplegics., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Background: A prototype solid-state Ultraviolet-C (UVC) LED device may be useful in the treatment of corneal microbial infections, as UVC is commonly used for eradicating bacteria, fungi and viruses in other settings. This study assessed the efficacy of 265 nm UVC from this LED, on four different bacterial strains, and investigated the consequences of corresponding exposures on human corneal epithelial cells in vitro., Methods: Agar plate lawns of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Streptococcus pyogenes were exposed to a 4.5 mm diameter 265 nm UVC beam at a fixed intensity and distance, for 30, 5, 4, 2 and 1 seconds. Growth inhibition was assessed with a BioRad Gel imager, and the diameter of lucent areas of bacterial inhibition recorded. Human corneal epithelial cells cultured on glass cover-slips were exposed to corresponding doses of UVC from the same device. Live/dead staining was performed and the results quantified., Results: There was 100% inhibition of growth for all bacteria tested, at all exposure times. A 30-second exposure of human corneal epithelium to UVC gave no statistically significant decrease (P = 0.877) in the ratio of live to dead cells when compared to control cultures., Conclusion: The results confirmed that a 1 second exposure to germicidal UVC from this LED source was sufficient to inhibit microbial proliferation in the four bacterial strains tested in vitro. The literature suggests UVC at this dose could potentially be beneficial in treating corneal surface infections, without causing significant adverse effects, supported by our findings in human corneal epithelium exposed to UVC., (© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.)

The reliability of the rabbit monoclonal antibodies SP1, SP2, SP3, and 4B5 was immunohistochemically assessed on a range of 96 invasive breast carcinomas and the results compared with those achieved with established antibody markers for estrogen receptors (6F11), progesterone receptors (PgR636), and HER2 (polyclonal A0485 and clone CB11), with HER2 status validated by fluorescence in situ hybridization (FISH) and silver in situ hybridization. Optimal results depended on the duration of microwave antigen-retrieval time and the use of a high pH buffer for rabbit and mouse estrogen receptor antibodies (SP1 and 6F11), although only on antigen-retrieval duration for the progesterone receptors SP2 and PgR636. The highest rate of concordance between HER2 overexpression and HER2 gene amplification was with the rabbit monoclonal antibodies (SP3 and 4B5) and FISH. Rabbit monoclonal antibodies are reliable alternatives to established antibody markers for the immunohistochemical testing of estrogen receptors, progesterone receptors, and HER2 in breast cancer.

Aim: The aim of this study was to attempt to visualize herpes simplex keratitis in an ex vivo model using currently available ophthalmological equipment and anti-herpes simplex virus 1 (HSV-1) fluorescein isothiocynate-labeled antibody., Methods: Sixteen donor human corneas were included in this study. Eight corneas were infected with HSV-1, whereas 8 remained uninfected. Abrasions were made on 2 infected and 2 uninfected corneas to assess a possible nonspecific absorption of antibodies in the sites of corneal epithelial defects. Corneas were examined before and after antibody application using a slit lamp, the fluorescein enhancing filter settings of fundus camera, and Confoscan 3. All corneas were further imaged using multiphoton laser confocal microscopy., Results: Before anti-HSV-1 antibody application, no fluorescence was detected in donor corneas with the blue light of the slit lamp and fundus camera at fluorescein enhancing filter settings. Examination with the fundus camera after antibody application detected increased background fluorescence in all the corneas with more highlighted areas of epithelial defects in abraded infected and uninfected corneas. Confoscan 3 did not show a significant difference between the appearances of HSV-1-infected and control corneas with and without application of the antibody. However, specific staining was confirmed by multiphoton laser confocal microscopy in all infected corneas., Conclusion: Further refinement of currently available ophthalmological tools is required to aid in vivo visualization of herpes simplex keratitis using fluorescein isothiocynate-labeled antibodies.

Ophthalmological pharmacology is a rapidly expanding field aimed at achieving the safest and most effective treatment results. Physicians must be aware of the side-effect profiles, both beneficial and harmful, of medications currently used. This review highlights the available data on the effect of some ophthalmic medications on pupil size; it was limited to all reports or studies describing topical ophthalmic agents not originally designed or indicated to alter pupil diameter. This awareness will protect patients from unwanted drug-induced side effects and will improve clinical management and patient care.

The advent of digital photography in the ophthalmic setting has provided not only a means of documenting pathology, but with instantaneous results, it is possible to aid clinical diagnosis and management. This study was designed to demonstrate the ability to image corneal epithelial lesions stained with fluorescein, with a digital fundus camera set on fluorescein angiography settings. The contrast of this technique demonstrated both gross and subtle corneal epithelial lesions better than traditional methods. The results obtained demonstrated the high sensitivity and high contrast images this technique can facilitate in every ophthalmic practice equipped with a fundus camera with digital fluorescein angiography capability.

The authors present a case of bilateral sequential extraocular muscle haematoma, for which no apparent cause has been identified despite extensive investigation, and which resolved without persisting morbidity. As far as the authors are aware, this is the first bilateral case to be reported.

Objective: To compare preparedness for hospital practice between graduates from a problem-based, graduate-entry medical program and those from other programs (undergraduate problem-based and traditional)., Design: Survey of graduates (by mailed questionnaire) and organisers of clinical training (by semistructured interview); results were compared with published results of surveys of graduates from other programs., Setting and Participants: All graduates of the first intake of the University of Sydney graduate-entry medical program were surveyed at the end of their first intern year (2001), along with the director of clinical training or intern manager at each of the New South Wales hospitals that employed the graduates., Main Outcome Measures: Graduates' self-reported level of preparedness in the eight domains of the Preparation for Hospital Practice Questionnaire; and organisers' opinions of their strengths and weaknesses., Results: 76 of 108 graduates from the graduate-entry program (70%) and organisers of clinical training at all 17 hospitals participated. Graduates from the program felt more prepared than did those from other programs in five of the eight domains assessed (interpersonal skills, confidence, collaboration, holistic care, and self-directed learning) and no less prepared in any domain. Organisers rated the graduates highly, especially in clinical competence, confidence, communication and professional skills. Opinions of interns' knowledge of basic sciences conflicted, with strengths and weaknesses mentioned with equal frequency., Conclusion: Graduates from the graduate-entry, problem-based program are at least as well prepared for their intern year as graduates from traditional and undergraduate problem-based programs.

Wounds of the skin heal in a predictable fashion and at a fairly constant rate if impediments to healing can be avoided. For the skin wound of the hand, the therapist and surgeon face paradoxic demands to balance optimal immobilization for wound healing with optimal motion for function. As long as the wound remains stable, therapy can begin very early in the postoperative period without interruption of the wound-healing process.

Pyoderma gangrenosum is an ulcerative cutaneous disorder that remains a diagnostic and therapeutic dilemma. Several medical therapies have been tried in treating the disorder. We report a patient with idiopathic pyoderma gangrenosum treated with the application of cultured epithelial autograft.

Intraperitoneal administration of the opiate antagonist, naloxone hydrochloride, resulted in decreased food and water consumption in drug-naive cats. In a cross-over Latin Square design, food consumed by six cats in a one hour period following 23 hours of deprivation, was decreased significantly below control (p less than 0.05) in linear relation to increasing dose (1 mg/kg and 10 mg/kg) of naloxone. Non-linear and time/order effects were not significant. Water consumption was decreased below control in a linear relation to increasing dose (1 and 10 mg/kg) for 5 of 6 cats at the 0.05 significance level. Non-linear and time/order effects on water consumption were not statistically significant for the same 5 cats. These results, and behavioral signs (i.e., vomiting, persistant vocalization, heavy salivation, mydriasis, moderate catatonia, and hissing) occasionally exhibited by four of the six cats in a 1-hr period following injection of the high dose, suggest a malaise-effect of naloxone.