Perivascular Basal Echogenicity in the Fetal Heart: An Unconventional Marker of Maternal Autoimmune Antibodies.

Fetal congenital heart block is a widely recognized complication of pregnancies with anti Ro/La antibodies. Less common presentations, including dilated cardiomyopathy, myocarditis, valvular insufficiency, and endocardial fibroelastosis, have also been described in these fetuses. We present two cases where recognition of isolated basal echogenicity of the fetal heart, an unconventional manifestation of anti-SSA antibodies during pregnancy, led to a suspicion and ultimately diagnosis of antibody positivity in the mother. These cases highlight the importance of being aware of this rare manifestation of anti-SSA antibodies during pregnancy, as early recognition of antibody positivity may lead to improve fetal and maternal outcomes.

Disparities in Use of Virtual Primary Care During the Early COVID-19 Pandemic.

Background: The COVID-19 pandemic increased the use of virtual health care. However, certain factors may disparately affect some patients' utilization of virtual care. Associations between age, racial categories (White or Black), and socioeconomic disadvantage were evaluated during the early COVID-19 pandemic. Methods: This cross-sectional retrospective study included adult patients with virtual or in-person primary care encounters at a large, midwestern hospital system with widespread urban and suburban offices between March 1, 2020, and June 30, 2020. Virtual visits included synchronous video and telephone visits and asynchronous patient portal E-visits. Chi-squared tests and multivariable logistic analysis assessed the associations between ages and racial categories, and area deprivation index with the use of virtual versus in-person primary care. Results: Of 72,153 patient encounters, 43.0% were virtual visits, 54.6% were White patients, and 45.4% were Black. Across equivalent age ranges, black patients were slightly less likely to utilize virtual care than similarly aged White patients, but not consistently across virtual modalities. Women were more likely to use virtual care across all modalities, and individuals >65 years were more likely to use telephone visits and less likely to use video and E-visits, regardless of race. Patients residing in areas with the greatest socioeconomic advantage were more likely to utilize video and E-visits. Conclusions: Differential patterns of utilization emerged across racial categories and age ranges, suggesting that racial disparities are exacerbated depending upon patient age and mode of utilization.

Cinnamic acid is beneficial to diabetic cardiomyopathy via its cardioprotective, anti-inflammatory, anti-dyslipidemia, and antidiabetic properties.

Diabetes-related health issues are increasing day by day in public, and diabetic cardiomyopathy (DCM) is one serious issue among them. There is a lack of proper strategy to control and manage DCM. Here we are attempting a nutraceutical-based approach to protect the heart from DCM. The beneficial effect of cinnamic acid (CiA), was evaluated in an experimental model of diabetes. For this, diabetic model was created by feeding male Wistar rats with a high fat, high fructose diet for 6 months and a single dose of streptozotocin (25 mg/kg bwt). Metformin was used as the positive control. The diabetic rats showed insulin resistance, myocardial injury, and a significant increase of total cholesterol, triglycerides, and LDL. Development of DCM was evident from the increased cardiac mass index, LDH, CKMB, ANP, and CRP levels in the diabetic group. There was a significant increase in the levels of cardiac hypertrophy markers like TGF-ß and ß-MHC in the hearts of diabetic rats revealing DCM. Pro-inflammatory cytokines (TNF-α, IL-6) and lipid peroxides were significantly elevated in the serum of diabetic rats. Histopathology revealed inflammation and necrosis in the heart of diabetic rats confirming DCM. Oral administration of CiA (5 and 10 mg/kg bwt) prevented the development of DCM via its cardioprotective, anti-inflammatory, anti-dyslipidemia potential, and antidiabetic properties. Similarly, metformin (50 mg/kg bwt) has also shown protection against DCM. We conclude from this study that CiA is found to be beneficial against DCM and recommend more detailed preclinical and clinical studies to develop CiA-based nutraceutical against DCM.

Using a Frontline Staff Intervention to Improve Cervical Cancer Screening in a Large Academic Internal Medicine Clinic.

BACKGROUND: Cervical cancer is the third most common malignancy affecting women. Screening with Papanicolaou (Pap) tests effectively identifies precancerous lesions and early-stage cervical cancer. While the nationwide rate of cervical cancer screening (CCS) is 84%, our urban general internal medicine (GIM) clinic population had a CCS rate of 70% in 2016. OBJECTIVE: To improve our clinic's CCS rate to match or exceed the national average within 18 months by identifying barriers and testing solutions. DESIGN: A quality improvement project led by a multidisciplinary group of healthcare providers. PARTICIPANTS: Our GIM clinic includes 16 attending physicians, 116 resident physicians, and 20 medical assistants (MAs) with an insured and underserved patient population. INTERVENTION: Phase 1 lasted 9 months and implemented CCS patient outreach, patient financial incentives, and clinic staff education. Phase 2 lasted 9 months and involved a workflow change in which MAs identified candidates for CCS during patient check-in. Feedback spanned the entire study period. MAIN MEASURES: Our primary outcome was the number of Pap tests completed per month during the 2 study phases. Our secondary outcome was the clinic population's CCS rate for all eligible clinic patients. KEY RESULTS: After interventions, the average number of monthly Pap tests increased from 35 to 56 in phase 1 and to 75 in phase 2. Of 385 patients contacted in phase 1, 283 scheduled a Pap test and 115 (41%) completed it. Compared to baseline, both interventions improved cervical cancer screening (phase 1 relative risk, 1.86; 95% CI, 1.64-2.10; P < 0.001; phase 2 relative risk, 2.70; 95% CI, 2.40-3.02; P < 0.001). Our clinic's CCS rate improved from 70% to 75% after the 18-month intervention. CONCLUSIONS: The rate of CCS increased by 5% after a systematic 2-phase organizational intervention that empowered MAs to remind, identify, and prepare candidates during check-in for CCS.

Low-dose steroid-induced bradyarrhythmias and treatment refractory hypokalaemia: a case report.

Corticosteroid therapy has become an important modality of treatment for diseases in which rapid control of immunoinflammatory processes is required. However, one of the serious, but less known adverse effect of this therapy is cardiac arrhythmias. This includes both tachyarrhythmias and bradyarrhythmias. Corticosteroid use may also be associated with electrolyte imbalances like hypokalaemia by its mineralocorticoid activity. Those side effects are mainly seen with high-dose intravenous methyl-prednisolone or oral pulse dose prednisolone therapy. Here we report our experience in a child with warm idiopathic autoimmune haemolytic anaemia who developed sinus bradyarrhythmias and treatment refractory hypokalaemia during low-dose steroid therapy with reduction in heart rate by 60% of baseline.

Functional Parcellation of the Cerebral Cortex Across the Human Adult Lifespan.

Adult aging is associated with differences in structure, function, and connectivity of brain areas. Age-based brain comparisons have typically rested on the assumption that brain areas exhibit a similar spatial organization across age; we evaluate this hypothesis directly. Area parcellation methods that identify locations where resting-state functional correlations (RSFC) exhibit abrupt transitions (boundary-mapping) are used to define cortical areas in cohorts of individuals sampled across a large range of the human adult lifespan (20-93 years). Most of the strongest areal boundaries are spatially consistent across age. Differences in parcellation boundaries are largely explained by differences in cortical thickness and anatomical alignment in older relative to younger adults. Despite the parcellation similarities, age-specific parcellations exhibit better internal validity relative to a young-adult parcellation applied to older adults' data, and age-specific parcels are better able to capture variability in task-evoked functional activity. Incorporating age-specific parcels as nodes in RSFC network analysis reveals that the spatial topography of the brain's large-scale system organization is comparable throughout aging, but confirms that the segregation of systems declines with increasing age. These observations demonstrate that many features of areal organization are consistent across adulthood, and reveal sources of age-related brain variation that contribute to the differences.

Inducing synesthesia in non-synesthetes: Short-term visual deprivation facilitates auditory-evoked visual percepts.

Sounds can modulate activity in visual cortex, facilitating the detection of visual targets. However, these sound-driven modulations are not thought to evoke conscious visual percepts in the general population. In individuals with synesthesia, however, multisensory interactions do lead to qualitatively different experiences such as sounds evoking flashes of light. Why, if multisensory interactions are present in all individuals, do only synesthetes experience abnormal qualia? Competing models differ in the time required for synesthetic experiences to emerge. The cross-activation model suggests synesthesia arises over months or years from the development of abnormal neural connections. Here we demonstrate that after ∼5 min of visual deprivation, sounds can evoke synesthesia-like percepts (vivid colors and Klüver form-constants) in ∼50% of non-synesthetes. These results challenge aspects of the cross-activation model and suggest that synesthesia exists as a latent feature in all individuals, manifesting when the balance of activity across the senses has been altered.

Indication for Dialysis Initiation and Mortality in Patients With Chronic Kidney Failure: A Retrospective Cohort Study.

BACKGROUND: Initiation of maintenance dialysis therapy for patients with chronic kidney failure is a period of high risk for adverse patient outcomes. Whether indications for dialysis therapy initiation are associated with mortality in this population is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 461 patients who initiated dialysis therapy (hemodialysis, 437; peritoneal dialysis, 24) from January 1, 2004, through December 31, 2012, and were treated in facilities operated by a single dialysis organization. Follow-up for the primary outcome was through December 31, 2013. PREDICTOR: Clinically documented primary indication for dialysis therapy initiation, as categorized into 4 groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown. OUTCOMES: All-cause mortality. RESULTS: During a median follow-up of 2.4 years, 183 (40%) patients died. Crude mortality rates were 10.0 (95% CI, 6.8-14.7), 12.7 (95% CI, 10.2-15.7), 21.7 (95% CI, 16.4-28.6), and 12.2 (95% CI, 6.8-14.7) deaths/100 patient-years among patients initiating dialysis therapy primarily for laboratory evidence of kidney function decline, uremic symptoms, volume overload or hypertension, and other/unknown reason, respectively. Following adjustment for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis therapy for uremic symptoms, volume overload or hypertension, or other/unknown reasons was associated with 1.12 (95% CI, 0.72-1.77), 1.69 (95% CI, 1.02-2.80), and 1.28 (95% CI, 0.73-2.26) times higher risk, respectively, for subsequent mortality compared to initiation for laboratory evidence of kidney function decline. LIMITATIONS: Possibility of residual confounding by unmeasured variables; reliance on clinical documentation to ascertain exposure. CONCLUSIONS: Patients initiating dialysis therapy due to volume overload may have increased risk for mortality compared with patients initiating dialysis due to laboratory evidence of kidney function decline. Further studies are needed to identify and test interventions that might reduce this risk.

Can follow-up phone calls improve patients self-monitoring of blood glucose?

AIMS AND OBJECTIVES: To evaluate the effectiveness of follow-up phone calls in improving frequency of glucose monitoring over a three month period in two groups of patients with type 2 diabetes with the goal to lower haemoglobin A1C. BACKGROUND: Telephone intervention has been successfully used in improving adherence to diabetes self-management and other chronic disease conditions. DESIGN: A quality improvement study. METHODS: Forty one Type 2 diabetic patients with HA1C ≥7·5% were included in the study. The patients were assigned to two groups. The first group of patients received standard diabetic care (Group 1) and the second group of patients (Group 2) received standard diabetic care plus follow-up phone calls within two weeks after a monthly clinic visit over a three month period. A haemoglobin A1C if indicated was done at the initial study visit. RESULTS: There were no statistically significant differences in the baseline haemoglobin A1C between the two groups or the three month haemoglobin A1C of the two groups. There were no statistically significant differences in mean haemoglobin A1C change between Group 1 and Group 2. The analysis revealed that there were no statistically significant differences between groups in the number of patients who kept logs of their blood glucose readings throughout the study. CONCLUSION: The intervention using telephone follow-up calls did not show a statistically significant improvement in overall HA1C, but there was a clinically significant change in HA1C in the group of patients that received follow-up phone calls. RELEVANCE TO CLINICAL PRACTICE: The clinical significance of the change in A1C in the follow-up phone call group (Group 2) supports that frequent contact by telephone may likely improve adherence to diabetes self-management.

Descending aortic flow reversal in obstructed total anomalous pulmonary venous connection.

In this study, we present the case of a neonate with obstructed infracardiac total anomalous pulmonary venous connection with severe pulmonary hypertension and a patent ductus arteriosus with right-to-left shunting. The patient had an unusual finding of pandiastolic flow reversal in the upper descending thoracic aorta. He underwent emergency surgical re-routing of the pulmonary veins to the left atrium, and postoperative echocardiography showed disappearance of the descending aortic flow reversal. We hypothesise that in severely obstructed total anomalous pulmonary venous connection the left ventricular output may be extremely low, resulting in flow reversal in the descending aorta.

Twin pregnancy in a Fontan-palliated patient.

The Fontan connection, originally described in 1971, is used to provide palliation for patients with many forms of CHDs that cannot support a biventricular circulation. An increasing number of females who have undergone these connections in childhood are now surviving into adulthood and some are becoming pregnant. We report a case of a 29-year-old woman who presented with a twin pregnancy at 33 weeks of gestation. She had significant deterioration of her cardiovascular status before the twin babies were delivered by emergency caesarean section owing to associated obstetric complications. This report also highlights the various maternal and fetal complications occurring in pregnancy of Fontan-palliated patients and suggests the need for meticulous pre-conception counselling and strict perinatal care.

Compartmentalized pressurization is a novel prognostic factor for hypercontractile esophagus.

BACKGROUND: Hypercontractile esophagus (HE) is a disorder of increased esophageal body contractile strength on high-resolution esophageal manometry (HREM). Compartmentalized pressurization (CP) is a pattern with an isobaric contour of >30 mmHg extending from the contractile front to the lower esophageal sphincter on HREM. The relevance of CP to HE has yet to be explored. METHODS: A retrospective review was performed on 830 HREM studies of patients to identify HE. HE patients' CP status and symptoms by Eckardt score (ES) were reviewed. Diagnoses were made using Chicago Classification (CC) v4.0. KEY RESULTS: Forty-seven patients (5.6%) were identified as having HE by CCv3, 30 (3.6%) of which had HE by CCv4. 11/30 HE patients had CP, and 19/30 did not. CP was associated with chronic opioid use (36.4% vs. 5.3% p = 0.047). Presenting ES was greater for HE patients with CP (7 vs. 4). Seven HE patients with CP and 11 without CP were managed medically. ES after medical therapy was higher in HE patients with CP compared to those without CP (9 vs. 0). No HE patients with CP responded to medical therapy. Kaplan-Meier analysis demonstrated significance of this association over time. 83% of all HE patients had all-cause symptom remission. CONCLUSIONS & INFERENCES: HE patients with CP are associated with a higher presenting ES. HE patients with CP do not respond to medical therapy, while HE patients without CP frequently do respond. CP in HE may have prognostic value in determination of treatment strategy for patients with HE.

Vanillic acid mitigates hyperinsulinemia induced ER stress mediated altered calcium homeostasis, MAMs distortion and surplus lipogenesis in HepG2 cells.

Hyperinsulinemia (HI) induced insulin resistance (IR) and associated pathologies are the burning and unsolvable issues in diabetes treatment. The cellular, molecular and biochemical events associated with HI are not yet elucidated. Similarly, no focused research on designing therapeutic strategies with natural products for attenuation of HI are seen in literature. Keeping this in mind we planned the present study to evaluate the alterations occurring at ER/Ca2+ homeostasis/mitochondria associated endoplasmic reticulum membranes (MAMs) in HepG2 cells during HI and to evaluate the possible beneficial effect of vanillic acid (VA) to mitigate the complications. An in vitro model of HI was established by treating HepG2 cells with human insulin (1 µM) for 24 h. Then, ER stress, Ca2+ homeostasis, MAMs, IR and hepatic lipogenesis were studied at protein level. Various proteins critical to ER, Ca2+ homeostasis and MAMs such as p-IRE-1α, ATF6, p-PERK, p-eIF2α, CHOP, XBP1, p-CAMKII, InsP3R, SERCA, JNK, GRP78, VDAC, Cyp D, GRP75, MFN2, PTEN and mTORC were studied and found altered significantly causing ER stress, defect in Ca2+ movements and distortion of MAMs. The decreased expression of IRS2 and an unaltered expression of IRS1 confirmed the development of selective insulin resistance in hepatocytes during HI and this was the crucial factor for the progression of the hepatic lipid accumulation. We found simultaneous treatment of VA is beneficial up to a certain extent to protect HepG2 cells from the adverse effect of HI via its antioxidant, antilipogenic, mitochondrial and ER protection properties.

Ferulic acid attenuates high glucose-induced MAM alterations via PACS2/IP3R2/FUNDC1/VDAC1 pathway activating proapoptotic proteins and ameliorates cardiomyopathy in diabetic rats.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the severe complications of diabetes with no known biomarkers for early detection. Mitochondria-associated endoplasmic reticulum membranes (MAM) are less studied subcellular targets but an emerging area for exploration in metabolic disorders including DCM. We herein studied the role of MAMs and downstream mitochondrial functions in DCM. We also explored the efficacy of ferulic acid (FeA) against DCM via modulation of MAM and its associated signaling pathway. METHODS: The H9c2 cardiomyoblast cells were incubated with high concentration (33 mM) of d-glucose for 48 h to create a high glucose ambience in vitro. The expression of various critical proteins of MAM, mitochondrial function, oxidative phosphorylation (OxPhos) and the genesis of apoptosis were examined. The rats fed with high fat/high fructose/streptozotocin (single dose, i.p.) were used as a diabetic model and analyzed the insulin resistance and markers of cardiac hypertrophy and apoptosis. RESULTS: High glucose conditions caused the upregulation of MAM formation via PACS2, IP3R2, FUNDC1, and VDAC1 and decreased mitochondrial biogenesis, fusion and OxPhos. The upregulation of mitochondria-driven SMAC-HTRA2-ARTS-XIAP apoptosis and other cell death pathways indicate their critical roles in the genesis of DCM at the molecular level. The diabetic rats also showed cardiomyopathy with increased heart mass index, TNNI3K, troponin, etc. FeA effectively prevented the high glucose-induced MAM alterations and associated cellular anomalies both in vitro and in vivo. CONCLUSION: High glucose-induced MAM distortion and subsequent mitochondrial dysfunctions act as the stem of cardiomyopathy. MAM could be explored as a potential target to treat diabetic cardiomyopathy. Also, the FeA could be an attractive nutraceutical agent for diabetic cardiomyopathy.

Biocompatible zeolite-dye composites with anti-amyloidogenic properties.

One of the most attractive approaches in biomedicine and pharmacy is the application of multifunctional materials. The mesoporous structure of clinoptilolite (CZ) absorbs various types of substances and can be used as a model for studying the carriers for targeted drug delivery with controlled release. CZ-dye composites are fabricated by incorporation into clinoptilolite pores commonly used dyes, aluminum phthalocyanine, zinc porphine, and hypericin. We examined and compared the effect of pure dyes and CZ-dye composites on insulin amyloidogenesis. The formation of insulin amyloid fibrils and the disassembly of preformed fibrils is significantly affected by any of the three compounds, however, the strongest effect is observed for aluminum phthalocyanine indicating a structurally-dependent anti-amyloidogenic activity of the dyes. The incorporation of dyes into CZ particles resulted in enhanced anti-amyloidogenic activity in comparison to pure CZ particles. The cell metabolic activity, biocompatibility and fluorescence biodistribution of the dyes entrapped in the composites were tested in vitro (U87 MG cells) and in vivo in the quail chorioallantoic membrane model. Considering the photoactive properties of the dyes used, we assume their applicability in photodiagnostics and photodynamic therapy. It can also be expected that their anti-amyloidogenic potential can be enhanced by photodynamic effect.

Categorization of collagen type I and II blend hydrogel using multipolarization SHG imaging with ResNet regression.

Previously, the discrimination of collagen types I and II was successfully achieved using peptide pitch angle and anisotropic parameter methods. However, these methods require fitting polarization second harmonic generation (SHG) pixel-wise information into generic mathematical models, revealing inconsistencies in categorizing collagen type I and II blend hydrogels. In this study, a ResNet approach based on multipolarization SHG imaging is proposed for the categorization and regression of collagen type I and II blend hydrogels at 0%, 25%, 50%, 75%, and 100% type II, without the need for prior time-consuming model fitting. A ResNet model, pretrained on 18 progressive polarization SHG images at 10° intervals for each percentage, categorizes the five blended collagen hydrogels with a mean absolute error (MAE) of 0.021, while the model pretrained on nonpolarization images exhibited 0.083 MAE. Moreover, the pretrained models can also generally regress the blend hydrogels at 20%, 40%, 60%, and 80% type II. In conclusion, the multipolarization SHG image-based ResNet analysis demonstrates the potential for an automated approach using deep learning to extract valuable information from the collagen matrix.

Clinical profile and predictors of therapeutic outcome with azithromycin in pediatric scrub typhus: A study from Eastern India.

In this prospective study, children from 1-month to 12-years, admitted with positive IgM ELISA testing for scrub typhus, were enrolled over 1-year and administered an empirical single dose of azithromycin (10 mg/kg). All 189 (median age 4.84-years) children had fever with median duration of 8 days at admission. Shortness of breath, altered sensorium, headache, lymphadenopathy, hepatosplenomegaly, pallor, oedema and hypotension were the most prominent symptoms/signs. About 46% of children developed complications, among them hepatic, neurological and cardiovascular were most common. Our study showed a remarkable response to azithromycin, with mean defervescence of 32 h and no mortality. The presence of shortness of breath, headache, altered sensorium, hepatosplenomegaly, meningeal signs, severe anemia, leucocytosis, hyponatremia along with/without any of above mentioned three systemic complications were independent predictors for delayed treatment response by multivariate logistic regression analysis. Hepatic, neurological and cardiovascular complications are an emerging trend. Empiric azithromycin based on clinical suspicion of scrub typhus can be lifesaving.

In vitro and in vivo studies reveal the beneficial effects of chlorogenic acid against ER stress mediated ER-phagy and associated apoptosis in the heart of diabetic rat.

Endoplasmic reticulum (ER) and associated signaling pathways are involved in diabetic cardiomyopathy (DCM) however, detailed studies are not available. The present study investigated the role of ER stress and related pathways such as ER-phagy, apoptosis and their underlying mechanisms using appropriate models. Beneficial effect of chlorogenic acid was also evaluated against ER stress mediated DCM. H9c2 cells with high glucose (33 mM, in vitro model of hyperglycemia) showed significant activation of ER stress response (GRP78, PERK, IRE1α, ATF6α) and altered its regulatory proteins (PDI, ERO1α). Also, it enhanced ER-phagy through upregulation of Sec62, RTN3 and downregulation of FAM134B. High glucose caused apoptosis via increased levels of CHOP, caspase 12 and calnexin. All these proteins (PERK, IRE1α, ATF6α, RTN3, Sec62 and FAM134B) have been found to have a significant role in the functioning of heart such as excitation contraction coupling and we expect these alterations to induce cardiomyopathy during diabetes. This was confirmed in in vivo study too. High fat, high fructose diet with mild streptozotocin induced diabetic rats showed an increased expression of BNP confirming cardiac injury. We also noticed severe ER stress in the heart of diabetic animals. All these have contributed significantly into alterations in histopathology and increase of weight of the hearts. These findings clearly show that ER stress plays a vital protagonist in the progression of DCM. We also found chlorogenic acid is effective against hyperglycemia induced pathological alteration both in vitro as well as in vivo.

Characterization of collagen response to bone fracture healing using polarization-SHG.

In this study, we extend on the three parameter analysis approach of utilizing a noninvasive dual-liquid-crystal-based polarization-resolved second harmonic generation (SHG) microscopy to facilitate the quantitative characterization of collagen types I and II in fracture healing tissues. The SHG images under various linear and circular polarization states are analyzed and quantified in terms of the peptide pitch angle (PA), SHG-circular dichroism (CD), and anisotropy parameter (AP). The results show that the collagen PA has a value of 49.26° after 2 weeks of fracture healing (collagen type II domination) and 49.05° after 4 weeks (collagen type I domination). Moreover, the SHG-CD and AP values of the different collagen types differ by 0.05. The change tendencies of the extracted PA, SHG-CD, and AP parameters over the healing time are consistent with the collagen properties of healthy nonfractured bone. Thus, the feasibility of the proposed dual-liquid-crystal-based polarization-SHG method for differentiating between collagen types I and II in bone fracture healing tissue is confirmed.