Can infrared light really be doing what we claim it is doing? Infrared light penetration principles, practices, and limitations.

Near infrared (NIR) light has been shown to provide beneficial treatment of traumatic brain injury (TBI) and other neurological problems. This concept has spawned a plethora of commercial entities and practitioners utilizing panels of light emitting diodes (LEDs) and promising to treat patients with TBI and other disorders, who are desperate for some treatment for their untreatable conditions. Unfortunately, an LED intended to deliver photonic energy to the human brain does not necessarily do what an LED pointed at a mouse brain does. There is a problem of scale. Extensive prior research has shown that infrared light from a 0.5-watt LED will not penetrate the scalp and skull of a human. Both the properties of NIR light and the manner in which it interacts with tissue are examined. Based on these principles, the shortcomings of current approaches to treating neurological disorders with NIR light are explored. Claims of clinical benefit from low-level LED-based devices are explored and the proof of concept challenged. To date, that proof is thin with marginal benefits which are largely transient. Extensive research has shown fluence at the level of the target tissue which falls within the range of 0.9 J/cm2 to 15 J/cm2 is most effective in activating the biological processes at the cellular level which underlie direct photobiomodulation. If low-level infrared light from LED devices is not penetrating the scalp and skull, then these devices certainly are not delivering that level of fluence to the neurons of the subjacent brain. Alternative mechanisms, such as remote photobiomodulation, which may underlie the small and transient benefits for TBI symptoms reported for low-power LED-based NIR studies are presented. Actionable recommendations for the field are offered.

Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications.

This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs.

Protocol for Imaging the Same Class IV Neurons at Different Stages of Development.

In this protocol, we focused on analyzing internal branches of Drosophila class IV neurons. These neurons are characterized by their highly branched axons and dendrites and intricately tile the larval body. As Drosophila larvae progress through developmental stages, the dendritic arbors of Class IV neurons undergo notable transformations. As Drosophila larvae develop, their Class IV dendritic arbors grow. In the initial 24 h after egg laying (AEL), the dendrites are smaller than segments. During the subsequent 24 h of the first instar larval stage, dendritic arbors outpace segment growth, achieving tiling. After 48 h, arbors and segments grow concurrently. Epidermal cells near Class IV dendrites expand in proportion to segment growth. This observation suggested that Class IV cells might grow via branch dilation-uniformly elongating branches, akin to Class I cells [1,2]. To understand whether the class IV complex arbor structure is formed by dilation or simply from growing tips, we developed this protocol to introduce a systematic approach for quantitatively assessing the growth dynamics of internal branches. Key features • This protocol employs imaging the same neuron over different development times • Drosophila embryo and larvae genotype is ;;ppkCD4-tdGFP, which explicitly tags class IV neurons • This protocol for the preparation of agar pads to mount and image Drosophila larvae is adapted from Monica Driscoll's method • Neurons are imaged without the use of anesthetics and for a short duration of time • This technique involves the use of a spinning disk confocal microscope.

Precision layering techniques: Integrating digital tools for accurate color matching and realistic try-ins in anterior composite restorations.

OBJECTIVE: This article aims to demonstrate the clinical application of a comprehensive workflow that integrates digital tools for accurate color matching, and its immediate implementation in the restoration of anterior teeth. CLINICAL CONSIDERATIONS: Two patients demonstrating dissatisfaction regarding a maxillary central incisor had an old restoration replaced resorting to a digital workflow to enhance the predictability of the new direct restoration. OptiShade allowed the precise assessment of tooth color and the CompoShade application provided precise color and material selection, as well as the determination of a layering strategy. Precision and accuracy of the colorimeter and the composite layering application were demonstrated clinically in vivo. CONCLUSIONS: Implementing a digital workflow with the integration of OptiShade measurements and the CompoShade layering recipe calculation, as well as the respective realistic try-in, enables the achievement of precise color matching for anterior composite restorations. CLINICAL SIGNIFICANCE: The employment of a digital colorimeter and layering recipes simplify shade matching, and optimizes composite resin clinical use and success. The implementation of a realistic try-in, previous to the definitive restoration, allows the clinician to perform any adjustments if needed.

Conservative Management of a Non-vital, Young, Permanent Tooth in a Pediatric Patient: A Case Report.

A fracture due to trauma in children is one of the most common traumas treated by dentists. Pain, swelling, and aesthetics are some of the most common chief complaints patients report to dental clinics after trauma. The anterior teeth play a significant role in the aesthetics of the patient's smile thus affecting the patient's psychological well-being. In addition, they are also important for mastication and speech. Treatment of fractured teeth, especially in the anterior region, has always been a major concern of aesthetics for the patient and the dentist. The most commonly observed fracture, i.e., Ellis class IV fracture includes endodontic treatment due to exposure of the pulp during trauma. This brief case report presents a case of an 11-year-old female with the chief complaint of a fractured tooth in the maxillary front teeth region. The treatment plan included the preventive procedures followed by root canal treatment and composite restoration with the right permanent maxillary lateral incisor. The benefit of this is directly linked to the professional's dexterity, skill, and technical mastery, as well as the achievement of desirable outcomes.

Maternal and perinatal outcomes in nulliparous women with a booking body mass index exceeding 50 kg/m2.

BACKGROUND: Women with a body mass index (BMI) >35 kg/m2 carry an increased obstetric risk; however, the experience of the Class IV and above obese nulliparous women is less understood. AIMS: To describe maternal and perinatal outcomes in nulliparous women of booking BMI > 50 kg/m2. MATERIALS AND METHODS: A cohort study of 48 nulliparous women who delivered between 2015 and 2019 in a tertiary hospital and had a booking BMI > 50 kg/m2. Obstetric outcome data was collated via electronic and written patient records. The relationship between mode of delivery and BMI was assessed using direct logistic regression. Multiple pregnancies and severe congenital malformations (n = 3) were excluded. RESULTS: The mean booking BMI was 53.7 kg/m2 (SD 4.05) and mean maternal age was 30.4 years (SD = 5.7). Comorbidities included asthma (43%), essential hypertension (20%) and diabetes (61%). Antenatally, accuracy was compromised in 80% of morphology scans (n = 35). In the perinatal period, 33 women (68.8%) were induced compared to a spontaneous onset of labour in two (4.1%) women. There were nine elective caesarean sections (CS), five of which were for breech presentation. Of those who intended on vaginal delivery (n = 35), 51% (n = 18) had an emergency CS. In these women, the risk of CS increased by a factor of 1.36 for every one point increase in BMI > 50 kg/m2. The average gestational age was 37.5 weeks (SD 2.4) with 14% (n = 6) experiencing preterm deliveries. The incidence of babies born >90th percentile for gestational age was 15 (34%). CONCLUSION: Increased BMI impairs maternal and perinatal outcomes and significantly increases the risk of emergency CS. BMI > 50 kg/m2 is associated with higher-level interventions and obstetric complications.

Early safety outcomes of laparoscopic one anastomosis gastric bypass in patients with class III, IV, and V obesity.

BACKGROUND: The extremely obese patient deserves special consideration: significant comorbidities, technical difficulties, and increased postoperative morbidity and mortality are all expected in this patient population. The study compared early postoperative complications (≤30-day) following one-anastomosis gastric bypass (OAGB) morbidity in patients with morbid obesity class IV obesity, body mass index (BMI) ≥50-59.9 kg/m2, and class V obesity, BMI ≥60 patients. METHODS: We retrospectively reviewed perioperative OAGB outcomes in three BMI groups. Operative time, length of stay (LOS), and overall early postoperative complication rates were studied. Patient-reported complications were ranked by Clavien-Dindo Classification (CDC). RESULTS: Between January 2017-December 2021, consecutive patients with obesity class III (n = 2950), IV (n = 256), and V (n = 23) underwent OAGB. BMI groups were comparable in sex, age, and associated comorbidities. Mean operative time was significantly longer in the higher BMI groups: class III (66.5 ± 25.6 min), IV (70.5 ± 28.7 min), and V (80.0 ± 34.7 min), respectively (p = 0.018); no difference in LOS. In respective BMI classes, ≤30-day complication rates were 3.2%, 3.5%, and 4.3% (p = 0.926). The respective number of patients with CDC grades of one to two were 45 (1.5%), 6 (2.3%), and 1 (4.3%), p = 0.500; and in grade ≥3a, 25 (0.8%), 1 (0.4%), 0 (0.0%), p = 0.669. There was 0.06% mortality (n = 2 in 3229), both in BMI class III. CONCLUSIONS: OAGB is a safe BS procedure in patients with class III, IV, and V obesity in the perioperative term with comparable ≤30-day morbidity in the three BMI groups.

An empirical predictive model for determining the aqueous solubility of BCS class IV drugs in amorphous solid dispersions.

CONTEXT: Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities. OBJECTIVE: This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices. METHODS: ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation. RESULTS: The ASDs' drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%. CONCLUSION: The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%.

Perinatal outcomes in women with class IV obesity compared to women in the normal or overweight body mass index categories: A population-based cohort study in Qatar.

Background: The prevalence of childhood and adult obesity is rising exponentially worldwide. Class IV obesity (body mass index, BMI ≥50 kg/m2) is associated with a higher risk of adverse perinatal outcomes. This study compared these outcomes between women with class IV obesity and women in the normal or overweight categories during pregnancy. Methods: A retrospective cohort study was performed in Qatar, including women having singleton live births beyond 24 weeks of gestation, classified into two class IV obesity and normal/overweight (BMI between 18.5 and 30.0 kg/m2). The outcome measures included the mode of delivery, development of gestational diabetes and hypertension, fetal macrosomia, small for date baby, preterm birth and neonatal morbidity. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were determined using multivariable logistic regression models. Results: A total of 247 women with class IV obesity were compared with 6797 normal/overweight women. Adjusted analysis showed that women with class IV obesity had 3.2 times higher odds of cesarean delivery (aOR: 3.19, CI: 2.26-4.50), 3.4 times higher odds of gestational diabetes (aOR: 3.39, CI: 2.55-4.50), 4.2 times higher odds of gestational hypertension (aOR: 4.18, CI: 2.45-7.13) and neonatal morbidity (aOR: 4.27, CI: 3.01-6.05), and 6.5 times higher odds of macrosomia (aOR 6.48, CI 4.22-9.99). Conclusions: Class IV obesity is associated with more adverse perinatal outcomes compared with the normal or overweight BMI categories. The study results emphasized the need for specialized antenatal obesity clinics to address the associated risks and reduce complications.

Renal Thrombotic Microangiopathy: A Complication of Paediatric Systemic Lupus Erythematosus That Requires Attention.

Systemic lupus erythematosus (SLE) is a multi-system disorder with a variety of clinical presentations. A wide range of renal vascular lesions (VL) is described predominantly in adult patients. The exact prevalence of renal VL in the pediatric SLE (pSLE) population is yet to be determined. A 10-year-old female patient with lupus nephritis (LN) presented with deteriorating kidney function. An exhaustive array of clinical-biochemical and pathological evaluations resulted in a diagnosis of class IV LN with thrombotic microangiopathy (TMA) associated with malignant hypertension and hypocomplementemia. Renal VL is overlooked or underreported in SLE patients, as it is neither accorded much importance in the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification nor in the activity and chronicity scoring. The TMA lesions in LN patients can be managed following the recently devised PLASMIC score; hence, reporting such VL has therapeutic implications.

A Nonrandomized Trial of the Effects of Near-Infrared Photobiomodulation Therapy on Bell's Palsy with a Duration of Greater Than 8 Weeks.

Objective: To determine whether photobiomodulation therapy (PBMT) by class IV Multiwave Locked System laser treatment as an adjunctive therapy could relieve symptoms in patients with Bell's palsy with a duration of greater than 8 weeks. Materials and methods: This nonrandomized controlled trial was conducted from January 2020 to December 2022. Patients were eligible if they had Bell's palsy with a duration of greater than 8 weeks at the out-patient department of otorhinolaryngology in Beijing Tongren Hospital. The control group consisted of patients recruited between January 1, 2020, and December 31, 2020. The PBMT group consisted of patients recruited between January 1, 2021, and December 31, 2022. In this study, the PBM used has a wavelength of 808 and 905 nm, 1.2 W power (808 nm is 1 W, 905 nm is 200 mW), continuous mode emission (808 nm) and pulsed mode emission (905 nm), 8.35 J/cm2 dosimetry, administered 3 times per week, 72 times of total treatment. The primary outcome measures included the House-Brackmann facial nerve grading system, the Sunnybrook facial grading system, and the Facial Clinimetric Evaluation Scale (FaCE). Secondary outcome measures comprised electroneurography, electromyography, and the blink reflex. Results: A total of 54 participants were included (27 in the control group and 27 in the photobiomodulation group). After 6 months, the House-Brackmann grading system [risk difference, -0.59, confidence interval (95% CI), -0.81 to -0.38, relative risk, 0.27, 95% CI, 0.13-0.56, p < 0.001], Sunnybrook facial grading system (21.14, 95% CI, 11.71-30.58; p < 0.001), and FaCE (-0.20, 95% CI, 0.41-0.02; p = 0.07) had significant difference between the two groups. Latency of ala nasi muscle (10.92, 95% CI, 5.58-16.27; p < 0.001) was not statistically significant after treatment compared with the control group; however, most of the electrophysiological examinations have significant difference between the two groups, respectively. Conclusions: The results of this study suggest that PBMT may relieve symptoms for patients with Bell's palsy with a duration of greater than 8 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT05585333.

A Survey of Retention and Support for Anterior Bounded Saddles of Removable Partial Dentures.

The treatment for the anterior bounded saddle because of missing teeth presents several challenges, primarily that of aesthetics. The choice of treatment depends on the position of the saddle, its size, the amount of available alveolar bone support, the health of the abutment teeth, and the patient's wishes.With regard to the use of a removable partial denture (RPD), while acknowledging the significant importance of aesthetics, unless the presence of adequate retention of the prosthesis is ensured, the appearance of the teeth alone will not guarantee its acceptability.This article highlights techniques that are available to provide adequate retention which will, in turn, give a patient confidence with the use of their denture. The techniques described are dependent on laboratory technical knowledge and skills, and on the ability of the patient to manipulate the appliance.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Clinicopathological, Immunological, and Laboratory Parameters of Childhood Lupus Nephritis: A Study from Northeast India.

Background Lupus nephrtis in children is associated with high morbidity and mortality. The incidence of childhood systemic lupus erythematosus (SLE) ranges from 3.3 to 8.8/100000 children with a higher Asian preponderance. The predominance of SLE in female pediatric patients increases gradually with age to the values observed in adults. Objectives To assess the clinical, immunological, and histopathological spectrum of childhood lupus nephritis in northeast India and explore the relationship between clinical, biochemical, serological, and histopathological findings. Materials and Methods A retrospective descriptive study was performed over 8 years. Histopathology slides were reviewed by two pathologists, whereas other details were collected from patients' records. Statistical Analysis Statistical analysis was based on the chi-square test and a p -value < 0.05 was considered statistically significant. Results Fifty-three cases of lupus nephritis were included in the study. The patients' age ranged from 5 to 18 years with a mean age of 14.5 years and a female: male ratio of 6.5:1. Edema and hypertension were the commonest clinical presentations, whereas proteinuria was the commonest presenting laboratory parameter. Amongst all the immunological markers, dsDNA was the commonest. Histopathologically, predominantly study population belonged to class IV lupus nephritis. The patients with class IV showed a statistically significant correlation with proteinuria and hematuria at the time of diagnosis. Immunological markers, namely, ANA and anti-ds-DNA positivity were significantly associated with advanced renal histopathology. Conclusion cSLE in northeast India presents mostly as Class IV LN presenting mostly with deranged laboratory parameters and preponderance of various immunological markers and clinical presentations.

A Three-step Etch-and-Rinse vs a Universal Adhesive in Nanohybrid Composite Anterior Restorations: A Retrospective Clinical Evaluation.

PURPOSE: To retrospectively evaluate the clinical behavior of direct anterior composite restorations performed with a universal adhesive or with a three-step etch-and-rinse (E&R) adhesive. MATERIAL AND METHODS: Patients were randomly treated with a three-step E&R adhesive (Optibond FL, Kerr) or a universal adhesive (Clearfil Universal Bond Quick, Kuraray Noritake) applied in E&R mode. All restorations were performed with a nanohybrid composite (ClearFil Majesty ES-2, Kuraray Noritake) by the same experienced operator. Two calibrated examiners evaluated the restorations using a dental mirror and explorer, in accordance with modified United States Public Health Service (USPHS) procedures. Clinical events were registered and classified as either failure (F), survival (SR), or success (S). RESULTS: 168 restorations were evaluated in 90 patients with an average follow-up period of 37.9 (± 22.9) months. A total of 132 restorations were performed on vital teeth, and 36 were performed on endodontically treated teeth (ETT). A total of 128 Class-IV and 40 Class-III restorations were performed. In 89 restorations, a three-step E&R adhesive was applied (14 Class-III and 75 Class-IV), while in 79, a universal adhesive was used (26 Class-III and 53 Class-IV, p = 0.0091). A Cox regression analysis was performed (p < 0.05) to analyze which factors were involved in the failure of the restorations, considering failure (F) as restorations that needed re-intervention at the follow-up period of 37.9 (± 22.9) months. No statistically significant differences were observed when considering parameters directly involved with the adhesives tested. Endodontically treated teeth were more prone to fractures (p = 0.0006) compared to vital teeth. Restorations made with universal adhesives failed by fracturing significantly more frequently (p = 0.0234), while restorations made on endodontically treated teeth had a significantly worse outcome (p = 0.0001). Restorations made on canines also failed significantly more frequently (HR = 3.8, 95% CI = 1.4-10.1, p = 0.0062). CONCLUSIONS: Based on the obtained results, both the universal adhesive and the three-step E&R adhesive proved to be good treatment choices for direct anterior restorations after 37.9 (± 22.9) months of follow-up. Tooth vitality seems fundamental for the prognosis of a direct anterior composite restoration over time.

Characterization of promoter elements of isoprene-responsive genes and the ability of isoprene to bind START domain transcription factors.

Isoprene has recently been proposed to be a signaling molecule that can enhance tolerance of both biotic and abiotic stress. Not all plants make isoprene, but all plants tested to date respond to isoprene. We hypothesized that isoprene interacts with existing signaling pathways rather than requiring novel mechanisms for its effect on plants. We analyzed the cis-regulatory elements (CREs) in promoters of isoprene-responsive genes and the corresponding transcription factors binding these promoter elements to obtain clues about the transcription factors and other proteins involved in isoprene signaling. Promoter regions of isoprene-responsive genes were characterized using the Arabidopsis cis-regulatory element database. CREs bind ARR1, Dof, DPBF, bHLH112, GATA factors, GT-1, MYB, and WRKY transcription factors, and light-responsive elements were overrepresented in promoters of isoprene-responsive genes; CBF-, HSF-, WUS-binding motifs were underrepresented. Transcription factors corresponding to CREs overrepresented in promoters of isoprene-responsive genes were mainly those important for stress responses: drought-, salt/osmotic-, oxidative-, herbivory/wounding and pathogen-stress. More than half of the isoprene-responsive genes contained at least one binding site for TFs of the class IV (homeodomain leucine zipper) HD-ZIP family, such as GL2, ATML1, PDF2, HDG11, ATHB17. While the HD-zipper-loop-zipper (ZLZ) domain binds to the L1 box of the promoter region, a special domain called the steroidogenic acute regulatory protein-related lipid transfer, or START domain, can bind ligands such as fatty acids (e.g., linolenic and linoleic acid). We tested whether isoprene might bind in such a START domain. Molecular simulations and modeling to test interactions between isoprene and a class IV HD-ZIP family START-domain-containing protein were carried out. Without membrane penetration by the HDG11 START domain, isoprene within the lipid bilayer was inaccessible to this domain, preventing protein interactions with membrane bound isoprene. The cross-talk between isoprene-mediated signaling and other growth regulator and stress signaling pathways, in terms of common CREs and transcription factors could enhance the stability of the isoprene emission trait when it evolves in a plant but so far it has not been possible to say what how isoprene is sensed to initiate signaling responses.

Comparison urine neutrophil gelatinase - associated lipocalin with standard parameters in monitoring activity Lupus nephritis: Class IV.

Background: Lupus nephritis (LN) is one of the most serious complications in the development of systemic lupus erythematosus, that can adversely affect the course and prognosis of this autoimmune disease. Therefore, monitoring the effect of applied therapy, achieving remission, or monitoring class IV LN activity is still a great challenge for nephrologists. This study aimed to compare the urinary neutrophile gelatinase associated lipocalin (u/NGAL) with traditionally accepted parameters for LNactivity to indicate the importance of its determination in these patients. Methods: The study group consisted of 40 patients with class IV LN, who were prospectively followed for a period of 4 months within three control visits to 2 months. The first group (20/40) had active disease (Group A), and the second group had diseasein remission (Group B). The parameters we monitored and compared at each visit were standard biochemical parameters and kidney function parameters: C-reactive protein (CRP), blood count (CBC), creatinine, total proteins, albumin, cholesterol, triglycerides, glomerular filtration rate (eGFR). Regarding immune parameters, complement C3 and C4, antinuclear antibodies (ANA), anti-double stranded DNA antibody(anti ds DNA Ab) were monitored. Urine sediment, proteinuria 24h, urine culture, urinary protein/creatinine ratio - Up/Cre, and urinary NGAL (u/NGAL) were monitored in. Results: Comparing standard parameters of disease activity and u/NGAL between groups, a statistically significant difference was obtained (p < 0.001). Within Group A, comparing the parameters by visits (0 : 2) for anti-ds-DNA Ab a significance of p< 0.05 was obtained, for albumin/s and C3 a significance of p<0.01 was obtained, and proteinuria/24h, Up/Cre, u/NGAL had a significance of p < 0.001. The mean level of u/NGAL was elevated at the initially visit (173.25 ± 172.12 ng/mL), after two months 73.2 ± 48.7 ng/mL, and in the second visit a lower level was recorded (49.60 ± 72.57 ng/mL). The negative correlation of u/NGAL was statistically significant at initial visit with albumin/s (p< 0.01) as well as the positive correlation with proteinuria 24h and Up/Cre (p< 0.001). In visit 2 significant negative correlation of u/NGAL with albumin/s and C3 p< 0.05, and positive correlation with anti-ds-DNA Ab, proteinuria 24h and Up/Cre p < 0.001. Conclusions: The results of our study indicate that the level of u/N GLA is elevated in patients with active Lupus nephritis class IV, as well as that it correlates with other parameters of disease activity. Serial determination of u/NGAL could be significant in monitoring disease course and treatment.

Safety and efficacy of MitraClip in acutely ill (NYHA Class IV) patients with mitral regurgitation: Results from the global EXPAND study.

AIM: Patients with severe mitral regurgitation (MR) and acute heart failure (HF) have refractory symptoms without adequate response to medical therapy. The objective of this analysis was to assess the impact of the MitraClip device in acutely ill HF patients, characterized by NYHA Class IV at baseline, in a real-world, contemporary setting. METHODS AND RESULTS: EXPAND was a prospective, multicenter, international study enrolling patients with MR who consented to receive the MitraClip System at 57 sites globally. The study outcomes included acute procedural success (APS), quality of life, heart failure hospitalizations (HFH), and all-cause mortality. The study population comprised 1,041 patients, with 118 patients having baseline NYHA Class IV, and 922 having baseline NYHA Class I/II/III. NYHA Class IV patients had a significantly higher rate of baseline co-morbidities and secondary MR aetiology compared with NYHA Class I/II/III patients. APS was achieved in 92.4% of NYHA Class IV patients and significant improvement in MR grade to ≤Mild (1+) in 90.7% of subjects at 30 days and 92.9% at 1 year was observed. 1-year-mortality was higher in the NYHA Class IV subjects compared with the NYHA Class I/II/III subjects (29.2% vs. 17.7%, P < 0.01). Significant improvement in functional capacity assessed by NYHA Functional Class and Quality of Life assessed through KCCQ score was observed. At 1 year, 72.6% of NYHA Class IV subjects improved to NYHA Class I/II and ΔKCCQ was 31.2 (24.1, 38.3) compared with baseline. CONCLUSION: In the prospective, real-world EXPAND study, MitraClip in patients with severe MR and NYHA Class IV was found to be safe and effective in treating MR, and significantly improving QoL and long-term clinical outcomes.

A Class IV Adenylate Cyclase, CyaB, Is Required for Capsule Polysaccharide Production and Biofilm Formation in Vibrio parahaemolyticus.

Cyclic AMP (cAMP) receptor protein (CRP), encoded by crp, is a global regulator that is activated by cAMP, a second messenger synthesized by a class I adenylate cyclase (AC-I) encoded by cyaA in Escherichia coli. cAMP-CRP is required for growth on nonpreferred carbon sources and is a global regulator. We constructed in-frame nonpolar deletions of the crp and cyaA homologs in Vibrio parahaemolyticus and found that the Δcrp mutant did not grow in minimal media supplemented with nonpreferred carbon sources, but the ΔcyaA mutant grew similarly to the wild type. Bioinformatics analysis of the V. parahaemolyticus genome identified a 181-amino-acid protein annotated as a class IV adenylate cyclase (AC-IV) named CyaB, a member of the CYTH protein superfamily. AC-IV phylogeny showed that CyaB was present in Gammaproteobacteria and Alphaproteobacteria as well as Planctomycetes and Archaea. Only the bacterial CyaB proteins contained an N-terminal motif, HFxxxxExExK, indicative of adenylyl cyclase activity. Both V. parahaemolyticus cyaA and cyaB genes functionally complemented an E. coli ΔcyaA mutant. The Δcrp and ΔcyaB ΔcyaA mutants showed defects in growth on nonpreferred carbon sources and in swimming and swarming motility, indicating that cAMP-CRP is an activator. The ΔcyaA and ΔcyaB single mutants had no defects in these phenotypes, indicating that AC-IV complements AC-I. Capsule polysaccharide and biofilm production assays showed significant defects in the Δcrp, ΔcyaBΔcyaA, and ΔcyaB mutants, whereas the ΔcyaA strain behaved similarly to the wild type. This is consistent with a role of cAMP-CRP as an activator of these phenotypes and establishes a cellular role for AC-IV in capsule and biofilm formation, which to date has been unestablished. IMPORTANCE Here, we characterized the roles of CRP and CyaA in V. parahaemolyticus, showing that cAMP-CRP is an activator of metabolism, motility, capsule production, and biofilm formation. These results are in contrast to cAMP-CRP in V. cholerae, which represses capsule and biofilm formation. Previously, only an AC-I CyaA had been identified in Vibrio species. Our data showed that an AC-IV CyaB homolog is present in V. parahaemolyticus and is required for optimal growth. The data demonstrated that CyaB is essential for capsule production and biofilm formation, uncovering a physiological role of AC-IV in bacteria. The data showed that the cyaB gene was widespread among Vibrionaceae species and several other Gammaproteobacteria, but in general, its phylogenetic distribution was limited. Our phylogenetic analysis also demonstrated that in some species the cyaB gene was acquired by horizontal gene transfer.

Management of Ellis Class-IV Fractured Tooth With an Open Apex: A Case Report.

Dental professionals face difficulty in managing "immature non-vital teeth with an open apex." It is considered to be challenging because, in this situation, root canal filling material should be confined within the boundaries of the root canal without extruding peri-apically. Apexification tries to create a hard tissue barrier that will cause the open apex to close, allowing root filling to be compacted. The current case report describes the application of mineral trioxide aggregate (MTA) to create an apical plug in an open apex, as MTA is considered a versatile material for apexification, which was followed by the reinforcing of the weekend root using glass fiber post and core build-up to manage the Ellis class IV fracture.