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.

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.

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.

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.

Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: The prevalence of hypertension and abnormal blood pressure (BP) patterns on 24-h ambulatory BP monitoring (ABPM) remains unknown in children with sickle cell disease (SCD). METHODS: Thirty-eight asymptomatic children with sickle cell disease (SCD) (12 HbSS receiving routine care, 13 HbSC, and 13 HbSS receiving chronic transfusion therapy) underwent 24-h ABPM. Average clinic BP, demographic and biochemical characteristics were collected. RESULTS: Median age was 13 years (range 11-16), body mass index (BMI) 19.1 kg/m(2) (range 18.2-21.1), and 50% were male. Seventeen subjects (43.6%) had ambulatory hypertension, while 4 (10.3%) were hypertensive based on their clinic BP. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) dip were 8.3 ± 5.9% and 14.7 ± 7.6% respectively. Twenty-three subjects (59%) had impaired SBP dipping, 7 (18%) had impaired DBP dipping, and 5 (13%) had reversed dipping. Clinic and ABP classification were modestly correlated (rho = 0.38, P = 0.02). CONCLUSION: Abnormalities in ABP measurements and patterns in children with SCD are prevalent and require more attention from heath care providers. ABPM is a valuable tool in identifying masked hypertension and abnormalities in circadian BP.

ISCEV standard for clinical pattern electroretinography (PERG): 2012 update.

The pattern electroretinogram (PERG) is a retinal response evoked by a contrast-reversing pattern, usually a black and white checkerboard, which provides information about macular and retinal ganglion cell function. This document from the International Society for Clinical Electrophysiology of Vision (www.iscev.org) is a scheduled revision of the ISCEV PERG Standard, which updates and replaces the 2007 update and all earlier versions. The standard defines a single minimum stimulus and recording protocol for clinical PERG testing to assist practitioners in obtaining good quality responses and to facilitate inter-laboratory comparison. The present revision tightens stimulus specifications, expands on steady-state PERG recording, addresses visual stimulus display distinctions (CRT vs. LCD), and provides a more explicit definition of response components.

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.

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.

Improvement in depression scores after 1 hour of light therapy treatment in patients with seasonal affective disorder.

The purpose of this study was to investigate possible rapid effects of light therapy on depressed mood in patients with seasonal affective disorder. Participants received 1 hour of bright light therapy and 1 hour of placebo dim red light in a randomized order crossover design. Depressed mood was measured at baseline and after each hour of light treatment using two self-report depression scales (Profile of Mood States-Depression-Dejection [POMS-D] subscale and the Beck Depression Inventory II [BDI-II]). When light effects were grouped for the two sessions, there was significantly greater reduction in self-report depression scores by -1.3 (p = 0.02) on the BDI-II and -1.2 (p = 0.02) on the POMS-D. A significant but modest improvement was detected after a single active light session. This is the first study, to our knowledge, to document an immediate improvement with light treatment using a placebo-controlled design with a clinical sample of depressed individuals.

Reading increases ocular illuminance during light treatment.

BACKGROUND: Bright-light treatment is a safe and effective treatment for the management of winter seasonal affective disorder (SAD). In a recent study, we found that the relative duration of reading was positively associated with likelihood of remission after six weeks of light treatment. METHODS: Two technicians measured the illuminance of a light box with a light meter directed towards the center of reading material that was placed on a table in front of the light box. The measurement was also performed after reading material was removed. The two measurements were performed in a randomized order. Friedman analysis of variance with Wilcoxon post-hoc tests were used to compare illuminance with vs. without reading. RESULTS: The presence of the reading material increased illuminance by 470.93 lux (95% CI 300.10-641.75), p<0.0001. LIMITATIONS: This is a technical report done under conditions intended to mimic those of typical ambulatory light treatment as much as possible. CONCLUSIONS: As reading materials reflect light from the light box, reading during light therapy increases ocular illuminance. If confirmed by future studies using continuous recordings in randomized design, instructing SAD patients to read during light therapy may contribute to a more complete response to light treatment. The downside of specific relevance for students, is that reading, in particular, with bright light in the late evening/early night may induce or worsen circadian phase delay, adversely affecting health and functioning.

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.

Diffuse retinal injury from a non-penetrating TASER dart.

To describe a non-penetrating TASER gun injury resulting in a small exudative retinal detachment but significant visual acuity and retinal function loss as demonstrated by electroretinography (ERG). A 39-year-old man presented to the emergency department with a TASER barb embedded in his right lower lid. A complete clinical ophthalmologic examination and surgical extrication were performed, as well as radiologic imaging and Ganzfeld electroretinography. No scleral penetration was observed on surgical exploration. Retinal examination showed a peripheral exudative detachment. Subsequent follow-up revealed progressive resolution of the detachment and improvement in visual acuity. The ERG showed a 63-70% decrease in rod a- and b-waves, while isolated cone responses were reduced by only 10%, with a minimal increase in implicit time. This case shows that periocular TASER injuries, even if apparently superficial, may result in significant ocular damage. ERG may be useful in the diagnosis of visual loss attributed to disturbance in photoreceptor function, in the absence of anatomically evident damage.

Evaluation of the antibacterial and anticancer activities of some South African medicinal plants.

BACKGROUND: Several herbs are traditionally used in the treatment of a variety of ailments particularly in the rural areas of South Africa where herbal medicine is mainly the source of health care system. Many of these herbs have not been assessed for safety or toxicity to tissue or organs of the mammalian recipients. METHODS: This study evaluated the cytotoxicity of some medicinal plants used, inter alia, in the treatment of diarrhoea, and stomach disorders. Six selected medicinal plants were assessed for their antibacterial activities against ampicillin-resistant and kanamycin-resistant strains of Escherichia coli by the broth micro-dilution methods. The cytotoxicities of methanol extracts and fractions of the six selected plants were determined using a modified tetrazolium-based colorimetric assay (3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay). RESULTS: The average minimum inhibitory concentration (MIC) values of the plants extracts ranged from 0.027 mg/mℓ to 2.5 mg/mℓ after 24 h of incubation. Eucomis autumnalis and Cyathula uncinulata had the most significant biological activity with the least MIC values. The in vitro cytotoxicity assay on human hepatocarcinoma cell line (Huh-7) revealed that the methanol extract of E. autumnalis had the strongest cytotoxicity with IC(50) of 7.8 µg/mℓ. Ethyl acetate and butanol fractions of C. uncinulata, Hypoxis latifolia, E. autumnalis and Lantana camara had lower cytotoxic effects on the cancer cell lines tested with IC(50) values ranging from 24.8 to 44.1 µg/mℓ; while all the fractions of Aloe arborescens and A. striatula had insignificant or no cytotoxic effects after 72 h of treatment. CONCLUSIONS: Our results indicate that the methanol fraction of E. autumnalis had a profound cytotoxic effect even though it possessed very significant antibacterial activity. This puts a query on its safety and hence a call for caution in its usage, thus a product being natural is not tantamount to being entirely safe. However, the antibacterial activities and non-cytotoxic effects of A. arborescens and A. striatula validates their continuous usage in ethnomedicine.

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.

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.

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.

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.

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.

Two novel CRX mutant proteins causing autosomal dominant Leber congenital amaurosis interact differently with NRL.

Leber congenital amaurosis (LCA) is a congenital retinal dystrophy characterized by severe visual loss in infancy and nystagmus. Although most often inherited in an autosomal recessive fashion, rare individuals with mutations in the cone-rod homeobox gene, CRX, have dominant disease. CRX is critical for photoreceptor development and acts synergistically with the leucine-zipper transcription factor, NRL. We report on the phenotype of two individuals with LCA due to novel, de novo CRX mutations, c.G264T(p.K74N) and c.413delT(p.I138fs48), that reduce transactivation in vitro to 10% and 30% of control values, respectively. Whereas the c.413delT(p.I138fs48) mutant allows co-expressed NRL to transactivate independently at its normal, baseline level, the c.G264T(p.K74N) mutant reduces co-expressed NRL transactivation and reduces steady state levels of both proteins. Although both mutant proteins predominantly localize normally to the nucleus, they also both show variable cytoplasmic localization. These observations suggest that some CRX-mediated LCA may result from effects beyond haploinsufficiency, such as the mutant protein interefering with other transcription factors' function. Such patients would therefore not likely benefit from a simple, gene-replacement strategy for their disease.