Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury.

Transcriptional profiling studies have identified several protective genes upregulated in tubular epithelial cells during acute kidney injury (AKI). Identifying upstream transcriptional regulators could lead to the development of therapeutic strategies augmenting the repair processes. SOX9 is a transcription factor controlling cell-fate during embryonic development and adult tissue homeostasis in multiple organs including the kidneys. SOX9 expression is low in adult kidneys; however, stress conditions can trigger its transcriptional upregulation in tubular epithelial cells. SOX9 plays a protective role during the early phase of AKI and facilitates repair during the recovery phase. To identify the upstream transcriptional regulators that drive SOX9 upregulation in tubular epithelial cells, we used an unbiased transcription factor screening approach. Preliminary screening and validation studies show that zinc finger protein 24 (ZFP24) governs SOX9 upregulation in tubular epithelial cells. ZFP24, a Cys2-His2 (C2H2) zinc finger protein, is essential for oligodendrocyte maturation and myelination; however, its role in the kidneys or in SOX9 regulation remains unknown. Here, we found that tubular epithelial ZFP24 gene ablation exacerbated ischemia, rhabdomyolysis, and cisplatin-associated AKI. Importantly, ZFP24 gene deletion resulted in suppression of SOX9 upregulation in injured tubular epithelial cells. Chromatin immunoprecipitation and promoter luciferase assays confirmed that ZFP24 bound to a specific site in both murine and human SOX9 promoters. Importantly, CRISPR/Cas9-mediated mutation in the ZFP24 binding site in the SOX9 promoter in vivo led to suppression of SOX9 upregulation during AKI. Thus, our findings identify ZFP24 as a critical stress-responsive transcription factor protecting tubular epithelial cells through SOX9 upregulation.

Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a very wide range of disease severity: from completely asymptomatic to fatal, and the reasons for that are not well understood; however, there are some data that show vitamin D may have a protective effect. METHODS: To retrieve the vitamin D levels data, the authors analyzed the vitamin D European population data compiled by 2019 European Calcified Tissue Society (ECTS) statement on vitamin D status published in the European Journal of Endocrinology. For the data set to be used for analysis, only recently published data that included general adult population of both genders aged 40-65 years or wider and must have included the prevalence of vitamin D deficiency. RESULTS: There were data sets from 10 countries that fitted the criteria and were analyzed. Severe vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million of population from coronavirus disease 2019 (COVID-19) and prevalence of severe vitamin D deficiency showed a strong correlation with r = 0.79, p = 0.007. Over time, correlation strengthened, and r coefficient asymptotically increased. After adjusting for countries' age structure and per capita health expenditures, multiple linear regression analysis showed that higher prevalence of severe vitamin D deficiency is associated with increased mortality. Each 1% increase in prevalence increased deaths by 55 per million (95% confidence interval, CI 8-102), p = 0.03. CONCLUSION: The authors recommend universal screening for vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.

Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe

BackgroundSARS-CoV-2 virus causes a very wide range of COVID-19 disease severity in humans: from completely asymptomatic to fatal, and the reasons behind it are often not understood. There is some data that Vitamin D may have protective effect, so authors decided to analyze European country-wide data to determine if Vitamin D levels are associated with COVID-19 population death rate. MethodsTo retrieve the Vitamin D levels data, authors analyzed the Vitamin D European population data compiled by 2019 ECTS Statement on Vitamin D Status published in the European Journal of Endocrinology. For the data set to used for analysis, only recently published data, that included general adult population of both genders ages 40-65 or wider, and must have included the prevalence of Vitamin D deficiency. ResultsThere were 10 countries data sets that fit the criteria and were analyzed. Severe Vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million from COVID-19 and prevalence of severe Vitamin D deficiency shows a strong correlation with r = 0.76, p = 0.01, indicating significant correlation. Correlation remained significant, even after adjusting for age structure of the population. Additionally, over time, correlation strengthened, and r coefficient asymptoticaly increased. ConclusionsAuthors recommend universal screening for Vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.

Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect.

OBJECTIVE: Opioids are frequently prescribed for chronic low back pain (CLBP), but there are broad individual differences in the benefits and risks of opioid therapy, including the development opioid-induced hyperalgesia. This study examined quantitative sensory testing (QST) data among a group of CLBP patients undergoing sustained oral opioid treatment. We investigated whether individual differences in psychological characteristics were related to opioid-induced changes in pain perception and pain modulation. DESIGN: The six-month, open-label trial evaluated patients with low to high levels of negative affect (e.g., symptoms of distress, depression and anxiety); participants underwent QST at baseline (prior to initiating treatment) and during oral opioid treatment. SETTING: A chronic pain management center. PATIENTS: The 31 study participants had chronic discogenic back pain, with a pain intensity rating >3/10. Participants were divided into groups with high vs. low levels of Negative Affect (NA). RESULTS: In the previously-published manuscript describing the clinical outcomes of the trial, high NA patients achieved only about half of the analgesic effect observed in the low NA group (Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 2015;123:861-72). The QST findings reported here suggested that tolerance to experimental (cold pressor) pain and conditioned pain modulation tended to decrease in the high NA group over the course of opioid treatment, while temporal summation of mechanical pain declined in the low NA group. CONCLUSIONS: These results reveal that while the low NA group seemed to exhibit a generally adaptive, analgesic pattern of changes during opioid management, the high NA group showed a pattern more consistent with opioid-induced hyperalgesic processes. A greater susceptibility to hyperalgesia-promoting changes in pain modulation among patients with high levels of distress may contribute to a lower degree of benefit from opioid treatment in high NA patients.

pH-metric chemical speciation modeling and studies of in vitro antidiabetic effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes.

A range of bidentate N,O-donor ligands of the imidazolyl-carboxylate moiety, which partially mimic naturally occurring bioligands, were prepared and reacted with the oxidovanadium(IV) ion to form the corresponding bis-coordinated oxidovanadium(IV) complexes. The aqueous pH-metric chemical speciation was investigated using glass electrode potentiometry, which allowed for the determination of protonation and stability constants of the ligands and complexes, respectively. The species distribution diagrams generated from this information gave evidence that the bis[(imidazolyl)carboxylato]oxovanadium(IV) complexes possess a broad pH-metric stability. The complexes improved glucose uptake in cell cultures using 3T3-L1 adipocytes, C2C12 muscle cells and Chang liver cells. The PTP inhibition studies indicated that the mechanism underlying insulin-stimulated glucose uptake was possibly via the protein tyrosine phosphorylation through the inhibition of the protein tyrosine phosphatase 1B (PTP 1B). The vanadium compounds also demonstrated the inhibition of D-dimer formation, suggesting that these compounds could potentially relieve a hypercoagulative state in diabetic patients.

Prevalence of Hepatitis B surface antigen among biomedical students of African descent in Usmanu Danfodiyo University, Sokoto, Nigeria.

BACKGROUND: Hepatitis B (HB) is a serious global public health problem that put health professionals particularly at risk. OBJECTIVE: The aim of this study was to investigate the prevalence of Hepatitis B surface antigen (HBsAg) among Biomedical Students of African descent attending Usmanu Danfodiyo University Sokoto in North-Western Nigeria. METHODS: The Onsite HBsAg (CTK Biotech, USA) was used to detect the presence of hepatitis B surface antigen. RESULTS: We tested 186 consecutively-recruited students consisting of 147 males and 39 females aged 18-35 years (mean age 26 ± 2.0 years). Of the 186 students tested, 25 (13.4%) were positive for HBsAg. The prevalence of HBsAg was significantly higher among students in the 21-25 years age group. Hepatitis B vaccination uptake among students was 7%. Majority of subjects were single 173(93.1%) compared to married 13 (6.9%). Ethnic distribution of the subjects indicated that 104(55.9%) were Hausa compared to Yoruba 32 (17.2%), other ethnic groups 21(11.3%), Fulani 20(10.8%) and Igbo 9(4.8%). CONCLUSIONS: This study indicates a high prevalence of hepatitis B virus infection among Biomedical students in Sokoto, North Western, Nigeria. Finding from this study is enough justification for the implementation of a policy to routinely test students entering into the biomedical professions for Hepatitis B virus infection. There is the need to provide hepatitis B vaccination universally to all those who are found negative prior to commencement of their biomedical training. There is also need to educate students entering biomedical professions and healthcare workers on the modes of transmission and prevention, importance of being compliant with protective vaccination as well as the need to observe universal precaution and infection control guidelines during their training and future professional practice.

When is a conservative approach best for proximal biceps tendon rupture?

This case demonstrates that when a patient's occupation and lifestyle do not require a high degree of supination and upper arm strength, conservative treatment may be the way to go.

Adaptive multiresolution analysis based on synchronization.

We propose an adaptive multiscale approach to data analysis based on synchronization. The approach is nonlinear, data driven in the sense that it does not rely on a priori chosen basis, and automatically determines the data scale. Numerical results for one- and two-dimensional cases illustrate that the method works effectively for the usual modulated signals such as chirps, etc., as well as for more complicated data with multiple scales. The method extends straightforwardly to functions defined on weighted graphs and grids in high dimensions. Connections with some other recent approaches to multiscale analysis are briefly discussed.

High frequency of PfCRT 76T in two Malian villages and its prevalence in severe relative to non-severe malaria.

We investigated PfCRT 76T mutation in severe and non-severe malaria in Southern Mali. One hundred and ninety three severe malaria cases were each matched against two non-severe malaria cases. Patients with G6PD deficiency and any known hemoglobin abnormality were excluded. PfCRT 76T was present in 60.8% (n=386) non-severe malaria cases and in 77.2% (n=193) severe malaria cases (p<0.0001). In children 5 years or younger, these proportions were 62.9% (n=294) vs. 73.5% (n=147), respectively (p<0.01). PfCRT 76T was therefore associated with malaria severity in this setting of Mali.

Overdose in infant caused by over-the-counter cough medicine.

Each year consumers purchase about 95 million units of over-the-counter medications for pediatric use, an unsafe application that can cause life-threatening effects. Despite a warning from the Food and Drug Administration, many parents or caregivers continue to administer these remedies to children. This report describes the case of a 4-month-old infant presenting to the emergency department with acute life-threatening intoxication including altered mental status, impaired coordination of movements, as well as a positive urine drug test for phencyclidine and an elevated serum ethanol level. Further evaluation uncovered that the actual reason for all clinical symptoms and laboratory test results was over-the-counter cough syrup.

Spatial symmetries in vestibular projections to the uvula-nodulus.

The discharge of secondary vestibular neurons relays the activity of the vestibular endorgans, occasioned by movements in three-dimensional physical space. At a slightly higher level of analysis, the discharge of each secondary vestibular neuron participates in a multifiber projection or pathway from primary afferents via the secondary neurons to another neuronal population. The logical organization of this projection determines whether characteristics of physical space are retained or lost. The logical structure of physical space is standardly expressed in terms of the mathematics of group theory. The logical organization of a projection can be compared to that of physical space by evaluating its symmetry group. The direct projection from the semicircular canal nerves via the vestibular nuclei to neck motor neurons has a full three-dimensional symmetry group, allowing it to maintain a three-dimensional coordinate frame. However, a projection may embed only a subgroup of the symmetry group of physical space, which incompletely mirrors the properties of physical space. The major visual and vestibular projections in the rabbit via the inferior olive to the uvula-nodulus carry three degrees of freedom-rotations about one vertical and two horizontal axes-but do not have full three dimensional symmetry. Instead, the vestibulo-olivo-nodular projection has symmetries corresponding to a product of two-dimensional vestibular and one-dimensional optokinetic spaces. This combination of projection symmetries provides the foundation for distinguishing horizontal from vertical rotations within a three dimensional space. In this study, we evaluate the symmetry group given by the physiological organization of the vestibulo-olivo-nodular projection. Although it acts on the same sets of elements and mirrors the rotations that occur in physical space, the physiological transformation group is distinct from the spatial group. We identify symmetries as products of physiological and spatial transformations. The symmetry group shapes the information the projection conveys to the uvula-nodulus; this shaping may depend on a physiological choice of generators, in the same way that function depends on the physiological choice of coordinates. We discuss the implications of the symmetry group for uvula-nodulus function, evolution, and functions of the vestibular system in general.

Converting relapsing remitting to secondary progressive experimental allergic encephalomyelitis (EAE) by ultraviolet B irradiation.

We induced experimental allergic encephalomyelitis (EAE) in SJL/J mice, an animal model for multiple sclerosis (MS), using myelin oligodendrocyte glycoprotein (MOG)(92-106) peptide, following ultraviolet (UV) irradiation. While all control mice developed relapsing-remitting (RR)-EAE, UV irradiation induced secondary progressive (SP)-EAE in some of the mice. Although mild demyelination was observed with T cell infiltration in RR-EAE, large demyelinating lesions developed in SP-EAE with massive macrophage and neutrophil infiltration and immunoglobulin deposition, but with little T cell infiltration. UV irradiation induced higher anti-MOG antibody responses. In SP-EAE, lymphoproliferative responses and interferon-gamma production were decreased without alteration of interleukin-4.

Metastatic prostate cancer to the spine and a PSA of 5666: a case report.

Prostate cancer is the most commonly diagnosed cancer and the second most common cause of cancer death among American men. To our knowledge, the highest reported prostate specific antigen (PSA) level on initial presentation is 3280 ng/mL. In this case report, we discuss a 46-year-old African-American man with back pain of 1-month's duration. A magnetic resonance imaging study of the lumbar spine revealed numerous osseous metastatic lesions, and the PSA level was found to be 5666 ng/mL. He was treated with oral narcotics and a Duragesic patch to achieve analgesia and bicalutamide (Casodex) and leuprolide acetate (Lupron) therapy for androgen blockade. Later in his course, he required chemotherapy due to hormone-refractory prostate cancer. The patient has done well as shown at his latest follow-up at 48 months. The objective of this report is to discuss the first patient with metastatic prostate cancer to the spine with PSA level greater than 3,500 ng/mL.

Osseous stress reaction in a rower diagnosed with positron emission tomography (PET): a case report.

Back injury is one of the most frequently encountered injuries in the collegiate rower. The differential diagnosis of back pain in the competitive rower includes muscle strain, ligament/tendon injury, stress reaction, stress fracture, and a tear in the annulus fibrosis. Endurance sports, such as rowing, have an increased frequency of stress injury The diagnosis of stress reaction cannot be made with plain radiographs. Many studies have firmly established the efficacy of single photon emission computed tomography (SPECT) bone scans and magnetic resonance imaging in establishing the diagnosis of a stress reaction We present a case of a collegiate rower with mid back pain secondary to a stress reaction of the endplates of the costotransverse articulation at the T8 level diagnosed by a positive positron emission tomogram study in the setting of a negative SPECT scan.

Strength post-spinal cord injury: myometer vs manual muscle test.

This study was designed to compare changes in strength after spinal cord injury (SCI) with the use of a hand held myometer to the manual muscle test (MMT). Eighty-eight C4-C8 Frankel A-D tetraplegic subjects were tested at various times up to 2 years post-SCI. Elbow flexor strength on successive examinations were grouped according to their early and later MMT scores (3.5 with no change in MMT. 3.5 to 4.0, and 3.5 to 4.5; 4.0 with no change in MMT, 4.0 to 4.5, and 4.0 to 5.0; 4.5 with no change in MMT, and 4.5 to 5.0). For each group, later myometric measurements (MYO) were expressed as percents of their earlier MYO and were analyzed using paired Student t-tests. Later MYO were 116, 205, 232% (P > 0.05, P < 0.002, P < 0.05) of their earlier MYO for groups 3.5 with no change in the MMT, 3.5 to 4.0, and 3.5 to 4.5 respectively. Later MYO were 140, 139, 191% (P < 0.05, P < 0.02, P < 0.0001) of their earlier MYO for groups 4.0 with no change in MMT, 4.0 to 4.5, and 4.0 to 5.0 respectively. Later MYO were 127 and 126% (P < 0.01, P < 0.02) of their earlier MYO for groups 4.5 with no change in MMT and 4.5 to 5.0 respectively. In conclusion the hand held myometer detected changes in muscle strength not detected by the MMT.