OBJECTIVE: This research aimed to improve diagnosis of non-alcoholic fatty liver disease (NAFLD) by deep learning with ultrasound Images and reduce the impact of the professional competence and personal bias of the diagnostician.
METHODS: Three convolutional neural network models were used to classify and identify the ultrasound images to obtain the best network. Then, the features in the ultrasound images were extracted and a new convolutional neural network was created based on the best network. Finally, the accuracy of several networks was compared and the best network was evaluated using AUC.
RESULTS: Models of VGG16, ResNet50, and Inception-v3 were individually applied to classify and identify 710 ultrasound images containing NAFLD, demonstrating accuracies of 66.2%, 58.5%, and 59.2%, respectively. To further improve the classification accuracy, two features are presented: the ultrasound echo attenuation coefficient (θ), derived from fitting brightness values within sliding region of interest (ROIs), and the ratio of Doppler effect (ROD), identified through analyzing spots exhibiting the Doppler effect. Then, a multi-input deep learning network framework based on the VGG16 model is established, where the VGG16 model processes ultrasound image, while the fully connected layers handle θ and ROD. Ultimately, these components are combined to jointly generate predictions, demonstrating robust diagnostic capabilities for moderate to severe fatty liver (AUC = 0.95). Moreover, the average accuracy is increased from 64.8% to 77.5%, attributed to the introduction of two advanced features with domain knowledge.
CONCLUSIONS: This research holds significant potential in aiding doctors for more precise and efficient diagnosis of ultrasound images related to NAFLD.

Iron-induced oxidative stress was thought to be the reason why the a-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present. It is assumed that reactive oxygen species (ROS) are generated in the presence of iron ions, and this leads to a decrease in hyperpolarization of the photoreceptor. It is known that in age-related macular degeneration (AMD), sodium iodate can induce oxidative stress, apoptosis, and retinal damage, which mimic the effects of clinical AMD. Here, the reduction of the a-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained.
The leading edge of the a-wave is divided into voltages developed by cones and rods. The same oxidative stress model is applied here since sodium iodate causes the creation of ROS in a manner similar to that caused by iron ions, with the exception that the retina is treated as a circuit of various resistances when computing the photoresponse. Moreover, sodium iodate also leads to apoptosis and, hence, may cause misalignment in cones (not in rods) during the initial stage of apoptosis in AMD. To include the effects of apoptosis and shortening in cones and rods, we have used a factor representing the fraction of total cones and rods that are alive. To include the effect of misalignment of cones on the reduction of the a-wave amplitude, we have used the Stiles-Crawford function to calculate the number of photoisomerizations occurring in a photoreceptor misaligned at an angle θ. The results are compared with experimental data.
In sodium iodate-treated eyes, the ROS produced can attract calcium ions in the photoreceptor, which increases the calcium influx. In the case of the cones, the inclusion of the misalignment angle in the phototransduction process helps in determining the voltage and slope of the voltage vs. time graph.The smaller the fraction of active photoreceptors, the smaller the amplitude of the a-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the a-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the a-wave to increase.
The reduction in the a-wave amplitude in the eyes of sodium iodate-treated mice is attributed to oxidative stress in both cones and rods and cone misalignment, which ultimately lead to apoptosis and vision loss in AMD.

Vertebrates rely on rod photoreceptors for vision in low-light conditions. Mammals have a specialized downstream circuit for rod signaling called the primary rod pathway, which comprises specific cell types and wiring patterns that are thought to be unique to this lineage. Thus, it has been long assumed that the primary rod pathway evolved in mammals. Here, we challenge this view by demonstrating that the mammalian primary rod pathway is conserved in zebrafish, which diverged from extant mammals ~400 million years ago. Using single-cell RNA-sequencing, we identified two bipolar cell (BC) types in zebrafish that are related to mammalian rod BCs (RBCs) of the primary rod pathway. By combining electrophysiology, histology, and ultrastructural reconstruction of the zebrafish RBCs, we found that, like mammalian RBCs, both zebrafish RBC types connect with all rods in their dendritic territory, and provide output largely onto amacrine cells. The wiring pattern of the amacrine cells post-synaptic to one RBC type is strikingly similar to that of mammalian RBCs, suggesting that the cell types and circuit design of the primary rod pathway have emerged before the divergence of teleost fish and amniotes. The second RBC type, which forms separate pathways, is either lost in mammals or emerged in fish.

Rod and cone photoreceptors in the retina of vertebrates are the primary sensory neurons underlying vision. They convert light into an electrical current using a signal transduction pathway that depends on Ca[Formula: see text] feedback. It is known that manipulating the Ca[Formula: see text] kinetics affects the response shape and the photoreceptor sensitivity, but a precise quantification of these effects remains unclear. We have approached this task in mouse retina by combining numerical simulations with mathematical analysis. We consider a parsimonious phototransduction model that incorporates negative Ca[Formula: see text] feedback onto the synthesis of cyclic GMP, and fast buffering reactions to alter the Ca[Formula: see text] kinetics. We derive analytic results for the photoreceptor functioning in sufficiently dim light conditions depending on the photoreceptor type. We exploit these results to obtain conceptual and quantitative insight into how response waveform and amplitude depend on the underlying biophysical processes and the Ca[Formula: see text] feedback. With a low amount of buffering, the Ca[Formula: see text] concentration changes in proportion to the current, and responses to flashes of light are monophasic. With more buffering, the change in the Ca[Formula: see text] concentration becomes delayed with respect to the current, which gives rise to a damped oscillation and a biphasic waveform. This shows that biphasic responses are not necessarily a manifestation of slow buffering reactions. We obtain analytic approximations for the peak flash amplitude as a function of the light intensity, which shows how the photoreceptor sensitivity depends on the biophysical parameters. Finally, we study how changing the extracellular Ca[Formula: see text] concentration affects the response.

Vertebrates rely on rod photoreceptors for vision in low-light conditions1. Mammals have a specialized downstream circuit for rod signaling called the primary rod pathway, which comprises specific cell types and wiring patterns that are thought to be unique to this lineage2-6. Thus, it has been long assumed that the primary rod pathway evolved in mammals3,5-7. Here, we challenge this view by demonstrating that the mammalian primary rod pathway is conserved in zebrafish, which diverged from extant mammals ~400 million years ago. Using single-cell RNA-sequencing, we identified two bipolar cell (BC) types in zebrafish that are related to mammalian rod BCs (RBCs) of the primary rod pathway. By combining electrophysiology, histology, and ultrastructural reconstruction of the zebrafish RBCs, we found that, like mammalian RBCs8, both zebrafish RBC types connect with all rods and red-cones in their dendritic territory, and provide output largely onto amacrine cells. The wiring pattern of the amacrine cells post-synaptic to one RBC type is strikingly similar to that of mammalian RBCs. This suggests that the cell types and circuit design of the primary rod pathway may have emerged before the divergence of teleost fish and amniotes (mammals, bird, reptiles). The second RBC type in zebrafish, which forms separate pathways from the first RBC type, is either lost in mammals or emerged in fish to serve yet unknown roles.

Rod and cone photoreceptors degenerate in inherited and age-related retinal degenerative diseases, ultimately leading to loss of vision. Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have shown a link between TH signaling and retinal degeneration. This work investigates the effects of excessive TH signaling on photoreceptor function and survival in mice. C57BL/6, Thra1 -/-, Thrb2 -/-, Thrb -/-, and the cone dominant Nrl -/- mice received triiodothyronine (T3) treatment (5-20 μg/ml in drinking water) for 30 d, followed by evaluations of retinal function, photoreceptor survival/death, and retinal stress/damage. Treatment with T3 reduced light responses of rods and cones by 50-60%, compared with untreated controls. Outer nuclear layer thickness and cone density were reduced by ∼18% and 75%, respectively, after T3 treatment. Retinal sections prepared from T3-treated mice showed significantly increased numbers of TUNEL-positive, p-γH2AX-positive, and 8-OHdG-positive cells, and activation of Müller glial cells. Gene expression analysis revealed upregulation of the genes involved in oxidative stress, necroptosis, and inflammation after T3 treatment. Deletion of Thra1 prevented T3-induced degeneration of rods but not cones, whereas deletion of Thrb2 preserved both rods and cones. Treatment with an antioxidant partially preserved photoreceptors and reduced retinal stress responses. This study demonstrates that excessive TH signaling induces oxidative stress/damage and necroptosis, induces photoreceptor degeneration, and impairs retinal function. The findings provide insights into the role of TH signaling in retinal degeneration and support the view of targeting TH signaling for photoreceptor protection.

Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.

Vertebrate rods and cones operate over a wide range of ambient illumination, which is provided by light adaptation mechanisms regulating the sensitivity and speed of the phototransduction cascade. Three calcium-sensitive feedback loops are well established in both rods and cones: acceleration of the quenching of a light-activated visual pigment and cGMP synthesis by guanylate cyclase, and increased affinity of ion channels for cGMP. Accumulating evidence suggests that the molecular mechanisms of light adaptation are more complex. While investigating these putative mechanisms, we discovered a novel phenomenon, observing that the recovery of light sensitivity in rods after turning off non-saturating adaptive light can take tens of seconds. Moreover, after a formal return of the membrane current to the dark level, cell sensitivity to the stimuli remains decreased for a further 1-2 min. We termed this phenomenon of prolonged photoreceptor desensitization \'adaptation memory\' (of previous illumination) and the current study is focused on its detailed investigation in rods and an attempt to find the same phenomenon in cones. In rods, we have explored the dependencies of this phenomenon on adapting conditions, specifically, the intensity and duration of adapting illumination. Additionally, we report that fish and frog red-sensitive cones possess similar features of adaptation memory, such as a drop in sensitivity just after the steps of bright light and slow sensitivity recovery. However, we have found that the rate of this process and its nature are not the same as in rods. Our results indicate that the nature of the temporary drop in the sensitivity in rods and cones after adapting steps of light is different. In the rods, adaptation memory could be attributed to the existence of long-lasting modifications of the components of the phototransduction cascade after adapting illumination. In cones, the observed form of the adaptation memory seems to be due to the sensitivity drop caused by a decrease in the availability of the visual pigment, that is, by bleaching.

The aim of this study was to determine the sociodemographic characteristics that affect job stress and job satisfaction in 454 healthcare workers (physicians, nurses, midwives, technicians, and other healthcare personnel) working with COVID-19 patients in primary healthcare institutions in Turkey with a cross-sectional, web-based survey between 9 and 30 August 2021. The survey included a personal information form, a standard job stress scale, and the Minnesota Satisfaction Questionnaire. The levels of job stress and job satisfaction did not differ between male and female respondents. Singles reported lower job stress and higher job satisfaction than the married respondents. Job stress did not differ between departments, but respondents on the front line who worked in a COVID-19 intensive care unit (ICU) (at any point and/or at the time of the study) or the emergency department reported lower job satisfaction than those working in other departments. Similarly, while stress did not differ by educational status, satisfaction of respondents with bachelor\'s or master\'s degree was lower than that of the rest. Our findings also suggest that working in a COVID-19 ICU and age are significant predictors of higher stress, whereas lower education, working in a COVID-19 ICU, and being married are good predictors of lower satisfaction. Further research should include other sociodemographic variables that may affect stress and satisfaction at work, and similar studies should follow up to see what was left in the wake of the pandemic.
Cilj je ovoga presječnog ispitivanja bio utvrditi sociodemografske karakteristike koje utječu na profesionalni stres i zadovoljstvo u 454 zaposlenika (liječnika, medicinskih sestara, bolničara, primalja, tehničara i drugih) u ustanovama primarne zdravstvene skrbi u Turskoj tijekom pandemije bolesti COVID-19. Ispitanici su od 9. do 30. kolovoza 2021. odgovarali na online upitnik, koji se sastojao od osobnih podataka, standardne ljestvice za ocjenu profesionalnoga stresa i od Minnesotskoga upitnika o zadovoljstvu. Razine profesionalnoga stresa i zadovoljstva nisu se razlikovale među spolovima. Ispitanici koji nisu u braku iskazali su niži stres i višu razinu zadovoljstva od onih u braku. U pogledu profesionalnoga stresa nije uočena razlika između odjela, ali su ispitanici na prvoj crti izloženosti, tj. oni koji su ikad radili ili rade s pacijentima oboljelima od bolesti COVID-19 na odjelu intenzivne njege (u trenutku ispunjavanja upitnika) odnosno na odjelu hitne pomoći, iskazali slabije zadovoljstvo poslom od ispitanika koji su radili na drugim odjelima. Isto tako nije bilo razlika u razinama stresa između ispitanika prema obrazovnom statusu, ali su ispitanici s najvišim obrazovanjem (bakalaureat, magisterij i više) iskazali slabije zadovoljstvo poslom od ostalih. Kad je o pretkazateljima stresa riječ, najznačajniji su rad na COVID-odjelu intenzivne njege i dob koji su, uz brak, također najznačajniji pretkazatelji nezadovoljstva poslom. Buduća bi istraživanja trebala obuhvatiti i druge sociodemografske varijable koje mogu utjecati na profesionalni stres i zadovoljstvo, a valjalo bi i nastaviti pratiti te parametre kako bi se vidjele promjene nakon proglašenja prestanka pandemije.

To determine the configuration of the distal fibula anatomy and the fitness of the Fibula Rod System (Acumed®, Hillsboro, Oregon) in a series of fibula models and to determine the optimal entry site of the rod.
Consecutive series of computed tomography (CT) of tibias and fibulae with no fracture or deformity were converted to stereo-lithograph format, and imported into Meshmixer software (Autodesk, San Rafael, California). A 3.6 × 180 mm fibula rod model was virtually inserted to best fit the intramedullary canal of the fibula model and to a depth of 0 mm proud at the distal fibula. The location of the entry point in relationship to the fibular tip, and the distance between the rod and the lateral fibula cortex were measured.
CT of 41 fibulae (23 male and 18 female patients) contributed to the three-dimensional fibula modeling. The entry point was 3.5 mm (SD 2.0) medial to (in mortise view) and 1.0 mm (SD 2.1) anterior to (in lateral view) the fibular tip. The fibula rod was inserted to a depth of 6.2 mm (SD 2.1) proximal to the fibula tip. The mean shortest distance of the rod to the outer cortex was 1.88 mm (SD 0.87). There was a breach of the posterolateral cortex in one patient.
The guide pin entry site of fibula rod should be medial and anterior offset with reference to the fibula tip, in contrary to the distal tip as recommended in the manual. There is a chance of breaching the posterolateral cortex with rod entry.