Autoimmune retinopathy in a patient with smoldering multiple myeloma: a case report.

PURPOSE: Multiple myeloma (MM) is a plasma cell dyscrasia leading to proliferation of monoclonal plasma cells. Ocular involvement in multiple myeloma is uncommon but can occur. The ocular manifestations of MM may include the cornea, uvea, and retinal vasculature. We present a rare case of autoimmune retinopathy associated with smoldering MM. CASE: A 76-year-old female with no significant past medical or ocular history presented with four months of worsening vision, difficulty with night driving, and loss of peripheral vision. Examination was notable for pallor of the optic nerves and vascular attenuation. Visual field testing demonstrated significant and progressive field loss in both eyes. An electroretinogram was extinguished under all conditions. Serum protein electrophoresis showed a significant elevation of IgG with an M-spike, and a subsequent bone marrow biopsy was performed showing 12.5% plasma cells, consistent with the diagnosis of MM. CAR antibody testing was positive for anti-enolase, anti-GAPDH, and anti-Rab6 antibodies, consistent with autoimmune retinopathy. DISCUSSION: Autoimmune retinopathy associated with MM is exceedingly rare. Management of this condition is challenging, as treatment of the underlying disease does not often lead to improvement in visual symptoms. Ultimately, visual prognosis is very poor, and both patients and clinicians should be aware of the guarded visual potential. CONCLUSION: The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients.

Isolation and genotypic characterization of extended-spectrum beta-lactamase-producing Escherichia coli O157:H7 and Aeromonas hydrophila from selected freshwater sources in Southwest Nigeria.

The proliferation of antibiotic-resistant bacteria and antimicrobial resistance is a pressing public health challenge because of their possible transfer to humans via contact with polluted water sources. In this study, three freshwater resources were assessed for important physicochemical characteristics as well as heterotrophic and coliform bacteria and as potential reservoirs for extended-spectrum beta-lactamase (ESBL) strains. The physicochemical characteristics ranged from 7.0 to 8.3; 25 to 30 °C, 0.4 to 93 mg/L, 0.53 to 8.80 mg/L and 53 to 240 mg/L for pH, temperature, dissolved oxygen (DO), biological oxygen demand (BOD5) and total dissolved solids, respectively. The physicochemical characteristics mostly align with guidelines except for the DO and BOD5 in some instances. Seventy-six (76) Aeromonas hydrophila and 65 Escherichia coli O157: H7 isolates were identified by preliminary biochemical analysis and PCR from the three sites. Among these, A. hydrophila displayed higher frequencies of antimicrobial resistance, with all 76 (100%) isolates completely resistant to cefuroxime and cefotaxime and with MARI ≥ 0.61. The test isolates showed more than 80% resistance against five of the ten test antimicrobials, with resistance against cefixime, a cephalosporin antibiotic being the highest at 95% (134/141). The frequency of the detection of the resistance genes in the A. hydrophila isolates generally ranged between 0% (blaSHV) and 26.3% (blaCTX-M), while the frequency of detection among the E. coli O157:H7 isolates ranged between 4.6% (blaCTX-M) and 58.4% (blaTEM). Our findings indicate that the distribution of antibiotic-resistant bacteria with diverse ESBL-producing capabilities and virulence genes in freshwater sources potentially threatens public health and the environment.

Uncemented total hip arthroplasty with a tapered titanium femoral component: a minimum 30-year follow-up.

The purpose of this study is to report our updated results at a minimum follow-up of 30 years using a first generation uncemented tapered femoral component in primary total hip arthroplasty (THA). The original cohort consisted of 145 consecutive THAs performed by a single surgeon in 138 patients. A total of 37 patients (40 hips) survived a minimum of 30 years, and are the focus of this review. The femoral component used in all cases was a first-generation Taperloc with a non-modular 28 mm femoral head. Clinical follow-up at a minimum of 30 years was obtained on every living patient. Radiological follow-up at 30 years was obtained on all but four. Seven femoral components (18%) required revision, and none for septic loosening. Four well fixed stems were removed during acetabular revision and three were revised for late infection. One femoral component (3%) was loose by radiological criteria. The mean Harris Hip Score improved from 47 points (SD 4.62) preoperatively to 83 points (SD 9.27) at final follow-up. With revision for any reason as the endpoint, survival of the femoral component was 80% (95% confidence interval (CI) 61% to 90%) at 32 years. With revision for aseptic loosing femoral component, survival was 99% (95% CI 93% to 99%). With regards to aseptic loosening, the Taperloc femoral component provides excellent fixation at a mean follow-up of 32 years.

Incidence of antibiotic resistance genotypes of Vibrio species recovered from selected freshwaters in Southwest Nigeria.

Vibrio species are classified as potent hazards because of their tendency to effect serious diseases like cholera and other gastrointestinal ailments in humans, as well as vibriosis in fish. A total of 144 freshwater samples were aseptically collected monthly across four rivers (Asejire, Ona, Dandaru and Erinle rivers) over a 12-month period from which Vibrio spp. were isolated using culture procedures, confirmed by means of biochemical test as well as Polymerase Chain Reaction (PCR) assay and further characterized for their phenotypic antibiotic susceptibilities and relevant antimicrobial resistant determinants by PCR. Three hundred and fifteen (58%) isolates confirmed across the sampled sites (Asejire = 75, Dandaru = 87, Eleyele = 72, Erinle = 81) showed high resistance against erythromycin-95%, Sulphamethoxazole-94%, rifampicin-92%, doxycycline-82%, tetracycline-75%, amoxicillin-45%, cephalothin-43% and varied susceptibilities to other antibiotics. The multiple antibiotic resistance indices of 97% of the Vibrio isolates were above the 0.2 threshold limit with MAR phenotype pattern E-SUL-RF-TET-DOX (0.38) found to be the most prevalent pattern among the isolates. The distributions of resistance determinant of the tested antibiotics were revealed as follows: sulII 33%, sulI 19% (sulfonamides); blaOXA 27%, ampC 39%, blapse 11% (beta-lactams); tetA 28%, tetE 20%, tet39 8%, (tetracyclines) and strA 39%. aacC2 24%, aphA1 14% (aminoglycosides). Strong positive associations were observed among tetA, sulI, tetE and sulII. This study raises concerns as these selected rivers may contribute to the environmental spread of waterborne diseases and antibiotic resistance genes. Therefore, we recommend environmental context-tailored strategies for monitoring and surveillance of resistance genes so as to safeguard the environment from becoming reservoirs of virulent and infectious Vibrio species.

Anti-NOGO Antibody Neuroprotection in a Rat Model of NAION.

Purpose: To evaluate the efficacy and mechanisms of anti-NOGO receptor monoclonal antibody 11C7mAb in a rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods: The rNAION was induced in one eye of 20 Long-Evans rats, which were studied in 10 groups of two rats, each group containing a sham rat receiving intravitreal injections of vehicle and a treatment rat receiving intravitreal injections of 11C7mAb. Fellow eyes served as naïve controls. The rats were tested using flash electroretinograms (ERGs), flash visual evoked potentials (VEPs), and optical coherence tomography (OCT). Thirty days after induction, they were euthanized, and the eyes were prepared for immunohistochemistry (two groups), hematoxylin and eosin staining (two groups) or transmission electron microscopy (TEM; six groups). Results: Ninety-five percent of the VEP amplitude was preserved in eyes treated with 11C7mAb, versus 69% in the control eyes. Immunohistochemistry revealed a large reduction in microglia and extrinsic macrophages with axon sparing. In addition to axon preservation, TEM also showed reduced extracellular debris and only slight myelin damage compared with the vehicle-treated animals. There were no significant differences in retinal ganglion cell counts, nor was there a difference in optic nerve swelling as measured by OCT. ERGs were used to exclude eyes with retinal vascular occlusions, an occasional complication of the induction technique. Conclusions: The 11C7mAb preserves optic nerve integrity and reduces inflammation in rNAION. Translational Relevance: This study evaluates the efficacy of an anti-NOGO receptor antibody in a rat model of NAION, a disorder that currently has no universally-acknowledged treatment.

Occurrence and antibiogram signatures of some Vibrio species recovered from selected rivers in South West Nigeria.

Vibrio species, widely distributed in water environments, has emerged as a prominent cause of water and food-related disease outbreaks posing significant risk to human and animal health worldwide. About 40% of presumptive isolates recovered from four selected rivers in Southwest Nigeria and, established as Vibrio species genus through polymerase chain reaction techniques., were subjected to antibiotic susceptibility testing against a panel of 18 commonly used antibiotics. The relative prevalence of key Vibrio species (V. parahaemolyticus, V. vulnificus, V. mimicus, V. harveyi, and V. cholerae) was in the order 17%, 13.3%, 4.4%, 2.2%, and 2.2% respectively. Antibiotic resistance by all Vibrio species was mostly observed against doxycycline (71-89%), erythromycin (86-100%), tetracycline (71-89%), rifampicin (86-100%), and sulfamethoxazole (87-100%), though susceptibility to meropenem (86-100%), cephalothin (60-100%), norfloxacin (93-100%), ciprofloxacin (88-100%), amikacin (64-100%), gentamicin (57-74%), and trimethoprim/sulfamethoxazole (57-81%) was equally observed in all species. Vibrio mimicus expressed highest resistance against streptomycin and chloramphenicol (64%), while V. vulnificus (52%) and V. cholerae (57%) had the highest resistance against cephalothin. High resistance against ampicillin (57%) and amoxicillin (50%) was exhibited by V. cholerae and V. mimicus respectively. Indexes of multiple antibiotic resistances (MARI) among Vibrio species ranged between 0.11 and 0.72 with the highest MAR index of 0.72 observed in one isolate of V. vulnificus. This study reveals high prevalence of Vibrio species in the selected rivers as well as elevated resistance against some first-line antibiotics, which suggests possible inappropriate antimicrobial usage around study communities. We conclude that the freshwater resources investigated are unfit for domestic, industrial, and recreational uses without treatment prior to use and are potential reservoirs of antibiotic-resistant Vibrio species in this environment.

Persistent Dark Cones in Oligocone Trichromacy Revealed by Multimodal Adaptive Optics Ophthalmoscopy.

Dark cone photoreceptors, defined as those with diminished or absent reflectivity when observed with adaptive optics (AO) ophthalmoscopy, are increasingly reported in retinal disorders. However, their structural and functional impact remain unclear. Here, we report a 3-year longitudinal study on a patient with oligocone trichromacy (OT) who presented with persistent, widespread dark cones within and near the macula. Diminished electroretinogram (ERG) cone but normal ERG rod responses together with normal color vision confirmed the OT diagnosis. In addition, the patient had normal to near normal visual acuity and retinal sensitivity. Occasional dark gaps in the photoreceptor layer were observed on optical coherence tomography, in agreement with reflectance AO scanning light ophthalmoscopy, which revealed that over 50% of the cones in the fovea were dark, increasing to 74% at 10° eccentricity. In addition, the cone density was 78% lower than normal histologic value at the fovea, and 20-40% lower at eccentricities of 5-15°. Interestingly, color vision testing was near normal at locations where cones were predominantly dark. These findings illustrate how a retina with predominant dark cones that persist over at least 3 years can support near normal central retinal function. Furthermore, this study adds to the growing evidence that cones can continue to survive under non-ideal conditions.

Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies.

Pre-operative low muscle mass is associated with major complications and lower recurrence-free survival after gastric cancer surgery.

BACKGROUND: Low muscle mass (LMM) has been associated with post-operative morbidity. This study aimed to examine the relationship between pre-operative LMM and major post-operative complications and survival in patients undergoing curative resection for gastric cancer. METHODS: A single-centre retrospective cohort study was conducted on consecutive patients who underwent surgical resection for gastric adenocarcinoma between 2008 and 2018. Patient demographics, radiological parameters, pathological data and complications were recorded. Skeletal muscle index was calculated using OsiriX software by manually measuring the cross-sectional skeletal muscle area at the third lumbar vertebra and correcting to the patient's height. Univariate and multivariate analyses were used to identify the risk factors associated with the outcomes. RESULTS: A total of 62 patients (36 males, mean age 68.3 ± 1.5 years) met the inclusion criteria. Twenty-six (41.9%) patients had LMM pre-operatively. Demographic data in the non-LMM and LMM groups were equally matched except for body mass index (27.6 ± 0.8 kg/m2 versus 24.3 ± 1.1 kg/m2 ; P = 0.012) and serum albumin (36.7 ± 0.7 g/L versus 33.8 ± 1.0 g/L; P = 0.017), which were higher in the non-LMM. LMM was associated with higher incidence of total (35.5% versus 64.5%; P = 0.006), minor (40% versus 60%; P = 0.030), major (9.1% versus 90.9%; P = 0.004) post-operative complications and decreased recurrence-free survival (hazard ratio 2.29; 95% confidence interval 1.10-4.77; P = 0.027). CONCLUSION: LMM is a significant independent risk factor for major post-operative complications and recurrence-free survival after gastrectomy. Pre-operative identification of LMM could be a useful tool for prognostication and may identify a group suitable for prehabilitation.

Health economic analysis of curative-intent gastrectomy for gastric carcinoma and the costs related to post-operative complications.

BACKGROUND: The management of post-gastrectomy complications requires considerable resources and is likely associated with a substantial economic burden. The objectives of this study were to perform a cost analysis of admissions following gastrectomy for gastric carcinoma and then to quantify the financial impact of post-operative complications. METHODS: A retrospective analysis was conducted in patients that underwent a gastrectomy from 2008 to 2019. Demographic data, operative information, post-operative complications and facility costs were compared. RESULTS: A total of 74 patients underwent a curative-intent gastrectomy during the study period. The 36 (48.6%) patients that had no complications had a median total admission cost of AU$29 228. A total of 21 (28.4%) patients had a minor complication and 17 (23.0%) patients had a major complication, with a median total admission cost of AU$36 592 and AU$71 808, respectively. The difference across all three groups was statistically significant. In patients who had major complications compared to those without complications, there was a significant increase in the cost of intensive care services, theatre resources and nursing care. Across the whole cohort, the principal cost centres accounting for the largest proportion of total cost were theatre equipment and resources (33.9%), nursing care on the ward (23.0%) and staffing time of the surgical team (16.7%). CONCLUSION: The surgical management of gastric cancer carries a substantial cost burden. The presence and severity of post-operative complications is strongly associated with increasing cost. Minimizing complications, in addition to obvious clinical benefits, enables a large reduction in costs of care.

Topical Trabodenoson Is Neuroprotective in a Rodent Model of Anterior Ischemic Optic Neuropathy (rNAION).

PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is the leading cause of sudden optic nerve-related vision loss currently without effective treatment. We evaluated the neuroprotective potential of ocular (topical) delivery of trabodenoson, a selective A1 receptor mimetic, in a rodent model of NAION (rNAION). METHODS: Daily topical delivery of 3% trabodenoson or vehicle administered in both eyes 3 days prior to rNAION induction and for 21 days post induction. Retinal appearance and optic nerve head (ONH) edema was evaluated using spectral-domain optical coherence tomography (SD-OCT). Retinal function was evaluated before and after induction by ganzfeld electroretinography (ERG). Brn3a(+) retinal ganglion cells (RGCs) were quantified by stereology. Axonal ultrastructure was evaluated by electron microscopy. RESULTS: Trabodenoson-treated eyes had significantly reduced optic nerve (ON) edema compared with vehicle-treated eyes (ANOVA, P < 0.05). Electrophysiologically, there was a nonsignificant trend toward b-wave and oscillatory potential (OP) preservation in the trabodenoson-treated eyes. RGC counts were higher in trabodenoson-treated eyes compared to vehicle (74% versus 47% of the contralateral eye; two-tailed t-test; P = 0.01), as were ON axons. No overt morphologic differences in cell inflammation were observed between vehicle- and trabodenoson-treated ONHs, but trabodenoson-treated ONHs revealed increased expression of astrocyte-related neuroprotective responses. CONCLUSIONS: Trabodenoson preserves RGCs in the rodent NAION model. While previous clinical trials focused on trabodenoson's ocular antihypertensive effect, our data suggest trabodenoson's primary target may be both the retina and ONH. Selective adenosine A1 agonists may prove an appropriate neuroprotective adjunctive for ischemia-related ON diseases such as NAION and glaucoma. TRANSLATIONAL RELEVANCE: RGC and ON neuroprotection in ischemic neuropathies may be achievable by topical administration of A1 adenosine agonists rather than by simply relying on intraocular pressure reduction.

An approach to revising mHealth interventions for children and families: A case example in sickle cell disease.

Frameworks for developing mHealth interventions that are informed by the end-user and improve accessibility are necessary to ensure interventions meet the needs of the intended population and advance the science of health behavior change. The approach described in this paper addresses a gap in the mHealth development literature by describing a step-by-step method for evaluating and revising the mHealth interventions for health behavior change in child-parent dyads. Furthermore, this approach introduces the Website Analysis and MeasureMent Inventory framework as an initial coding structure for analyzing qualitative data to gauge appeal and enhance engagement of intervention for end-users. This method uses specific considerations for child-parent dyads and details an example in the development and refinement of a mobile application for self-management in children with sickle cell disease. This approach is translatable to populations of children with other chronic conditions and to other health behaviors.

ISCEV extended protocol for the stimulus-response series for the dark-adapted full-field ERG b-wave.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum protocol for clinical testing but encourages more extensive testing where appropriate. This ISCEV extended protocol describes an extension of the ISCEV full-field ERG standard, in which methods to record and evaluate the growth of the dark-adapted (DA) ERG b-wave with increasing stimulus energy are described. The flashes span a range that includes the weakest flash required to generate a reliable DA ERG b-wave and that required to generate a maximal b-wave amplitude. The DA ERG b-wave stimulus-response series (also known historically as the "intensity-response" or "luminance-response" series) can more comprehensively characterize generalized rod system function than the ISCEV standard ERG protocol and may be of diagnostic or prognostic value in disorders that cause generalized rod system dysfunction.

Incidence and antimicrobial susceptibility fingerprints of Plesiomonas shigelliodes isolates in water samples collected from some freshwater resources in Southwest Nigeria.

Plesiomonas shigelloides, is an emerging and significant enteric pathogen in water having implication in both localised and gastrointestinal infections with characteristic of displaying high resistance against commonly used antibiotics. This study evaluated the prevalence of Plesiomonas shigelloides and their antibiogram fingerprints in water sample collected from four rivers in South-western Nigeria. In all, 148 presumptive Plesiomonas shigelloides isolates was recovered from the rivers out of which 66 (44.6%) were confirmed positive for the organism using polymerase chain reaction techniques. Confirmed isolates were evaluated for their antibiogram profiles against a panel of 20 antimicrobials using the disc diffusion method and further screened for relevant antibiotic resistance genes. Resistance of the isolates against the antimicrobials followed the order: sulphamethoxazole (100%), erythromycin (93%), ampicillin (90%), cephalotin (82%), streptomycin (64%), and chloramphenicol (58%), amoxicillin (53%), cefotaxime (50%), tetracycline (49%), neomycin (38%) and trimethoprim + sulphamethoxazole (38%). Conversely, all the isolates were susceptible against netilmicin, and susceptibility against the other antibiotics follows the order: meropenem (94%), gentamicin (88%), imipenem (79%), amikacin (70%), ciprofloxacin (70%), norfloxacin (59%), trimethoprim (56%) and ceftazidine (56%). The multiple antibiotic resistance indices of the organism were higher than the accepted threshold of 0.2. The incidence of 11 antimicrobial resistance determinants were obtained as follows: [sulphonamides; (sulI (18%), sulII (20%), dfr1 (70%), dfr(18) (5%)), [beta-lactams; (ampC 37%)], [tetracyclines; (tetA (78%), tetE (57%)], [phenicols; (catII (16%), cmlA1 (11%)] and [aminoglycosides; (aphA2 (36%) and strA (67%)]. Pearson chi-square exact test revealed positive associations among tetA, tetE, sullI and catII and tetA genes. To the best of our knowledge, this is the first report on the incidence and antibiogram fingerprint of P. shigelloides in these freshwater resources and we conclude that these rivers are important reservoirs of multiple antimicrobial resistant biotypes of this organism, and consequently a threat to public health.

Early outcomes of two-stage minimally invasive oesophagectomy in an Australian institution.

BACKGROUND: Minimally invasive oesophagectomy (MIO) has a steep learning curve. We report our outcomes of a standardized 25 mm circular-stapled anastomosis using a trans-orally placed anvil (Orvil™). The objective of this study is to report the initial experience of introducing two-stage MIO to an Australian tertiary health service. METHODS: We describe our consecutive case series of all MIOs performed from a prospectively maintained database. We assessed the morbidity and mortality of MIO at our institution. We compared our first 30 cases to the second cohort of 32 cases. RESULTS: There were 62 two-stage MIOs performed from 2011 to 2015. The average age was 65 years. Median length of stay was 13 days (5-72 days). Median number of total lymph nodes was 14. Conversion occurred in three patients (5%). Major morbidity was 45%. Delayed gastric emptying 6% (n = 4), pneumonia 6% (n = 4), chyle leak 6% (n = 4), pulmonary embolus 2% (n = 1) and grade II or III anastomotic leak 5% (n = 4). One conduit ischaemia (2%) required reoperation and formation of oesophagostomy. There was one post-operative death within 30 days. There were five post-oesophagectomy hiatal hernias requiring re-operation (8%). There was a significant improvement in operative time (minutes) from the first to second cohort 588 versus 464 (P-value 0.01). CONCLUSION: The introduction of two-stage MIO to the Australian setting can be safely instituted. Our unit was still within a learning curve after 30 cases.

Prediction of outcome of bright light treatment in patients with seasonal affective disorder: Discarding the early response, confirming a higher atypical balance, and uncovering a higher body mass index at baseline as predictors of endpoint outcome.

BACKGROUND: We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. METHODS: Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. RESULTS: No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. LIMITATIONS: Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. CONCLUSION: Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms.

Antibacterial activity of crude extracts of some South African medicinal plants against multidrug resistant etiological agents of diarrhoea.

BACKGROUND: This study evaluated the antibacterial activity of some plants used in folklore medicine to treat diarrhoea in the Eastern Cape Province, South Africa. METHODS: The acetone extracts of Acacia mearnsii De Wild., Aloe arborescens Mill., A. striata Haw., Cyathula uncinulata (Schrad.) Schinz, Eucomis autumnalis (Mill.) Chitt., E. comosa (Houtt.) Wehrh., Hermbstaedtia odorata (Burch. ex Moq.) T.Cooke, Hydnora africana Thunb, Hypoxis latifolia Wight, Pelargonium sidoides DC, Psidium guajava L and Schizocarphus nervosus (Burch.) van der Merwe were screened against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, multi-resistant Salmonella enterica serovar Isangi, S. typhi, S. enterica serovar Typhimurium, Shigella flexneri type 1b and Sh. sonnei phase II. A qualitative phytochemical screening of the plants extracts was by thin layer chromatography. Plants extracts were screened for antibacterial activity using serial dilution microplate technique and bioautography. RESULTS: The TLC fingerprint indicated the presence of terpenoids and flavonoids in the herbs. Most of the tested organisms were sensitive to the crude acetone extracts with minimum inhibitory concentration (MIC) values ranging from 0.018-2.5 mg/mℓ. Extracts of A. striata, C. uncinulata, E. autumnalis and P. guajava were more active against enteropathogens. S. aureus and Sh. flexneri were the most sensitive isolates to the crude extracts but of significance is the antibacterial activity of A. arborescens and P. guajava against a confirmed extended spectrum betalactamase positive S. enterica serovar Typhimurium. CONCLUSION: The presence of bioactive compounds and the antibacterial activity of some of the selected herbs against multidrug resistant enteric agents corroborate assertions by traditional healers on their efficacies.

Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy.

INTRODUCTION: Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment. METHODS: NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION. RESULTS: Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats. CONCLUSIONS: Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.

Peripapillary Retinal Nerve Fiber Layer Swelling Predicts Peripapillary Atrophy in a Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy.

PURPOSE: To determine the relationship between peripapillary retinal nerve fiber layer (PRNFL) swelling and eventual PRNFL atrophy, and between PRNFL swelling/atrophy and neural function, in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (pNAION). METHODS: pNAION was induced in five normal, adult male rhesus monkeys by laser activation of intravenously injected rose bengal at the optic nerve head. Spectral-domain optical coherence tomography measurements of the PRNFL were performed at baseline; 1 day; 1, 2, and 4 weeks; and several later times over a period of an additional 2 to 3 months. Simultaneous pattern-reversal electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded and color fundus photographs taken at the same time points. RESULTS: In all cases, initial PRNFL swelling was associated with atrophy, and the greater the initial swelling, the greater the degree of eventual atrophy (r = 0.65, P = 0.0002). The change in PRNFL thickness closely correlated with VEP amplitude loss (r = 0.90), although this relationship was only a strong trend (P = 0.083). Furthermore, VEP amplitude loss closely correlated with PERG N95 amplitude loss (r = 0.80, P = 0.00002). CONCLUSIONS: In our model of human NAION, the degree of initial PRNFL swelling correlated with the severity of atrophy. Areas that did not swell developed little to no atrophy. The amount of PRNFL loss was reflected in VEP and PERG N95 amplitude reductions.

PERSISTENT RETINAL CHANGES AFTER INTRAVITREAL OCRIPLASMIN.

BACKGROUND/PURPOSE: Postmarket analysis helps identify potentially important side effects not discovered during clinical trials. Ocriplasmin is a recently approved medication administered by intravitreal injection for the treatment of symptomatic vitreomacular adhesion and macular hole. Overall, clinical trials of ocriplasmin have shown a relatively high safety profile. However, recently, a series of case reports have highlighted acute vision loss associated with abnormal findings on spectral domain optical coherence tomography and electroretinography. METHODS/RESULTS: A 70-year-old man developed multiple discrete pockets of macular subretinal fluid 10 weeks after intravitreal ocriplasmin injection, with minimal resolution of fluid over 11 months. Electroretinographic findings demonstrated persistent rod photoreceptor sensitivity loss at 14 months after injection. CONCLUSION: This is the first report of persistent electroretinographic and optical coherence tomographic abnormalities after ocriplasmin injection. Electroretinography abnormalities were noted in a small percentage of patients during ocriplasmin clinical trials and in a recent series of case reports and postmarket survey analysis. The authors propose that cleavage of fibronectin and laminin causes disruption of the interphotoreceptor matrix, leading to the ellipsoid layer attenuation and resultant electroretinographic sensitivity loss and subretinal fluid described on spectral domain optical coherence tomography. Persistent changes over 14 months in this patient indicate that ocriplasmin may have the potential to cause permanent retinal damage.