Management of Pilonidal Disease and Hidradenitis Suppurativa.

Pilonidal disease and hidradenitis suppurativa affect healthy young adults, causing discomfort and pain that leads to loss of work productivity and should be approached in a personalized manner. Patients with pilonidal disease should engage in hair removal to the sacrococcygeal region and surgical options considered. Hidradenitis suppurativa can be a morbid and challenging disease process. Medical management with topical agents, antibiotics, and biologics should be used initially but wide local excision should be considered in severe or refractory cases of the disease.

Comparative Analysis of Techniques for Pit and Fissure Sealant Application to Reduce Microleakage.

Introduction In modern dentistry, the focus is more on preventing caries than on treating it, which helps preserve the tooth structure. Pit and fissure sealants (PFS) are the most effective methods for providing a mechanical barrier and avoiding the accumulation of dental plaque in deep pits and fissures, thereby preventing occlusal caries. The present study was conducted to compare the efficiency of dentin bonding agents (DBA) with or without fissurotomy in reducing microleakage before PFS placement. Materials and methods A total of 48 freshly extracted premolars were randomly divided into four groups as follows: Group 1, the conventional technique of PFS (Clinpro, 3M ESPE sealant); Group 2, fissurotomy performed before PFS placement; Group 3, Scotchbond Universal Adhesive (3M ESPE DBA) applied before PFS placement; and Group 4, fissurotomy along with DBA was used before PFS placement. The teeth were subjected to thermocycling followed by dye penetration using a 1% solution of methylene blue for 24 hours. All teeth were then assessed for microleakage by a qualitative method using a stereomicroscope at 40X and depth of dye penetration by image analysis. The Kruskal-Wallis test followed by Dunn's test was used for intergroup comparisons of microleakage scores, and ANOVA followed by Tukey's test was used for intergroup comparisons of the depth of dye penetration. These analyses were conducted using statistical software (SPSS version 22, Chicago, IL, USA). Results Statistically significant differences were observed between the groups in terms of the microleakage scores and depth of dye penetration (p<0.05). The group 4 showed a minimum microleakage score (0.50±0.52), and maximum scores were observed in Group 1 (2.16±0.71). Group 2 showed insignificant differences with groups 3 and 4 for depth of dye penetration (p>0.05). Statistically significant differences were observed between groups 1 and 2, groups 1 and 4, and groups 3 and 4 for the microleakage score (p<0.05). Conclusion Fissurotomy with or without DBA significantly reduced microleakage before the PFS placement. Prior use of fourth-generation DBA significantly reduced microleakage compared with PFS placement without the use of DBA.

Targeting ABCG1 and SREBP-2 mediated cholesterol homeostasis ameliorates Zika virus-induced ocular pathology.

Zika virus (ZIKV) infection during pregnancy causes severe neurological and ocular abnormalities in infants, yet no vaccine or antivirals are available. Our transcriptomic analysis of ZIKV-infected retinal pigment epithelial (RPE) cells revealed alterations in the cholesterol pathway. Thus, we investigated the functional roles of ATP binding cassette transporter G1 (ABCG1) and sterol response element binding protein 2 (SREPB-2), two key players in cholesterol metabolism, during ocular ZIKV infection. Our in vitro data showed that increased ABCG1 activity via liver X receptors (LXRs), reduced ZIKV replication, while ABCG1 knockdown increased replication with elevated intracellular cholesterol. Conversely, inhibiting SREBP-2 or its knockdown reduced ZIKV replication by lowering cholesterol levels. In vivo, LXR agonist or SREBP-2 inhibitor treatment mitigated ZIKV-induced chorioretinal lesions in mice, concomitant with decreased expression of inflammatory mediators and increased activation of antiviral response genes. In summary, our study identifies ABCG1's antiviral role and SREBP-2's proviral effects in ocular ZIKV infection, offering cholesterol metabolism as a potential target to develop antiviral therapies.

Pseudohypoaldosteronism Type II or Gordon Syndrome: A Rare Syndrome of Hyperkalemia and Hypertension With Normal Renal Function.

Pseudohypoaldosteronism type II (PHA II) or Gordon syndrome is characterized by hyperkalemia, hypertension, hyperchloremic metabolic acidosis, low plasma renin activity, and normal kidney function. We report a rare case of a young adult female patient presenting with abdominal pain, diarrhea, and vomiting. She was hypertensive during the presentation. Blood work showed mild anemia, hyperkalemia, hyperchloremia, and metabolic acidosis, with normal renal function and liver function. Plasma renin activity and aldosterone levels were low-normal. These findings were suggestive of PHA II or Gordon syndrome. It is a rare familial disease, with a non-specific presentation and no specific diagnostic criteria, and physicians should suspect it in patients with hyperkalemia in the setting of normal glomerular filtration, along with hypertension (which can be absent), metabolic acidosis, hyperchloremia, low plasma renin activity, and relatively suppressed aldosterone.

A case of mediastinal hyperparathyromatosis.

Recurrent hyperparathyroidism (HPT) after initial parathyroid surgery occurs rarely in an ectopic location. The rare phenomenon of parathyromatosis may be the cause of this. We present the case of a 59-year-old woman with recurrent HPT, which presented as a new ectopic mediastinal parathyroid gland 13 years after initial 3.5 gland parathyroidectomy. A 1.5 × 1.3 cm lesion was discovered as an incidental finding in the pretracheal region, closely abutting the aortic arch. An aspirate revealed oncocytic cells, which were positive for parathyroid hormone, confirming a mediastinal parathyroid nodule. Sestamibi scan confirmed an avid nodule in the mediastinum. This patient had multiple co-morbidities but was asymptomatic of HPT. It was therefore decided at multi-disciplinary team discussion that she should undergo surveillance. To our knowledge, no such presentations have been reported in the literature. Thus, our case report is a unique addition of an atypical presentation of HPT.

In-depth investigations into symmetrical labyrinthine acoustic metamaterial with two micro-slit entries for low-frequency sound absorption.

Sound absorption below 1000 Hz has been extremely difficult through traditional barriers and absorbers, but it is required for noise control of appliances and machineries. Existing passive acoustic metamaterials attenuate low-frequency noise but with narrow bandwidths and bulky sizes. Hence, this paper proposes an acoustic metamaterial with enclosed symmetrical labyrinthine air channels and two micro-slits (configuration 1, identical slits; configuration 2, unequal length slits) at the end channels. Its theoretical model is established by acoustic impedance analysis using electro-acoustic analogy and validated numerically and experimentally. Sound absorption is found to happen as a result of impedance matching, Fabry-Perot-like labyrinthine resonances, and thermo-viscous losses in micro-slits. Parametric investigations reveal that increase in the number of channels, channel length, total height, and outer panel thickness shifts sound absorption peak to lower frequency but also decreases the magnitude and frequency range of absorption. Decreasing the channel width and slit width increases the sound absorption magnitude without changing absorption frequencies. Interestingly, unequal slit lengths perform better than equal slits by giving a lower frequency sound absorption with increased magnitude and frequency range, which is unlike that in existing labyrinthine metamaterials. Therefore, the proposed unequal slit metamaterial has enhanced low-frequency sound absorption and can be applied to appliances and machineries.

Heterozygosity in factor XIII genes and the manifestation of mild inherited factor XIII deficiency.

BACKGROUND: The characterization of inherited mild factor XIII deficiency is more imprecise than its rare, inherited severe forms. It is known that heterozygosity at FXIII genetic loci results in mild FXIII deficiency, characterized by circulating FXIII activity levels ranging from 20% to 60%. There exists a gap in information on 1) how genetic heterozygosity renders clinical bleeding manifestations among these individuals and 2) the reversal of unexplained bleeding upon FXIII administration in mild FXIII-deficient individuals. OBJECTIVES: To assess the prevalence and burden of mild FXIII deficiency among the apparently healthy German-Caucasian population and correlate it with genetic heterozygosity at FXIII and fibrinogen gene loci. METHODS: Peripheral blood was collected from 752 donors selected from the general population with essentially no bleeding complications to ensure asymptomatic predisposition. These were assessed for FXIII and fibrinogen activity, and FXIII and fibrinogen genes were resequenced using next-generation sequencing. For comparison, a retrospective analysis was performed on a cohort of mild inherited FXIII deficiency patients referred to us. RESULTS: The prevalence of mild FXIII deficiency was high (∼0.8%) among the screened German-Caucasian population compared with its rare-severe forms. Although no new heterozygous missense variants were found, certain combinations were relatively dominant/prevalent among the mild FXIII-deficient individuals. CONCLUSION: This extensive, population-based quasi-experimental approach revealed that the burden of heterozygosity in FXIII and fibrinogen gene loci causes the clinical manifestation of inherited mild FXIII deficiency, resulting in ''unexplained bleeding'' upon provocation.

Reconstitution of the phosphodiesterase 6 maturation process important for photoreceptor cell function.

The sixth family phosphodiesterases (PDE6) are principal effector enzymes of the phototransduction cascade in rods and cones. Maturation of nascent PDE6 protein into a functional enzyme relies on a coordinated action of ubiquitous chaperone HSP90, its specialized cochaperone aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), and the regulatory Pγ-subunit of PDE6. Deficits in PDE6 maturation and function underlie severe visual disorders and blindness. Here, to elucidate the roles of HSP90, AIPL1, and Pγ in the maturation process, we developed the heterologous expression system of human cone PDE6C in insect cells allowing characterization of the purified enzyme. We demonstrate that in the absence of Pγ, HSP90, and AIPL1 convert the inactive and aggregating PDE6C species into dimeric PDE6C that is predominantly misassembled. Nonetheless, a small fraction of PDE6C is properly assembled and fully functional. From the analysis of mutant mice that lack both rod Pγ and PDE6C, we conclude that, in contrast to the cone enzyme, no maturation of rod PDE6AB occurs in the absence of Pγ. Co-expression of PDE6C with AIPL1 and Pγ in insect cells leads to a fully mature enzyme that is equivalent to retinal PDE6. Lastly, using immature PDE6C and purified chaperone components, we reconstituted the process of the client maturation in vitro. Based on this analysis we propose a scheme for the PDE6 maturation process.

Naphthyl bearing 1,3,4-thiadiazoleacetamides targeting the parasitic folate pathway as anti-infectious agents: in silico, synthesis, and biological approach.

Malaria is still a complex and lethal parasitic infectious disease, despite the availability of effective antimalarial drugs. Resistance of malaria parasites to current treatments necessitates new antimalarials targeting P. falciparum proteins. The present study reported the design and synthesis of a series of a 2-(4-substituted piperazin-1-yl)-N-(5-((naphthalen-2-yloxy)methyl)-1,3,4-thiadiazol-2-yl)acetamide hybrids for the inhibition of Plasmodium falciparum dihydrofolate reductase (PfDHFR) using computational biology tools followed by chemical synthesis, structural characterization, and functional analysis. The synthesized compounds were evaluated for their in vitro antimalarial activity against CQ-sensitive PfNF54 and CQ-resistant PfW2 strain. Compounds T5 and T6 are the most active compounds having anti-plasmodial activity against PfNF54 with IC50 values of 0.94 and 3.46 µM respectively. Compound T8 is the most active against the PfW2 strain having an IC50 of 3.91 µM. Further, these active hybrids (T5, T6, and T8) were also evaluated for enzyme inhibition assay against PfDHFR. All the tested compounds were non-toxic against the Hek293 cell line with good selectivity indices. Hemolysis assay also showed non-toxicity of these compounds on normal uninfected human RBCs. In silico molecular docking studies were carried out in the binding pocket of both the wild-type and quadruple mutant Pf-DHFR-TS to gain further insights into probable modes of action of active compounds. ADME prediction and physiochemical properties support their drug-likeness. Additionally, they were screened for antileishmanial activity against L. donovani promastigotes to explore broader applications. Thus, this study provides molecular frameworks for developing potent antimalarials and antileishmanial agents.

Fingolimod (FTY720), an FDA-approved sphingosine 1-phosphate (S1P) receptor agonist, restores endothelial hyperpermeability in cellular and animal models of dengue virus serotype 2 infection.

Extensive vascular leakage and shock is a major cause of dengue-associated mortality. At present, there are no specific treatments available. Sphingolipid pathway is a key player in the endothelial barrier integrity; and is mediated through the five sphingosine-1-phosphate receptors (S1PR1-S1PR5). Signaling through S1PR2 promotes barrier disruption; and in Dengue virus (DENV)-infection, there is overexpression of this receptor. Fingolimod (FTY720) is a specific agonist that targets the remaining barrier-protective S1P receptors, without targeting S1PR2. In the present study, we explored whether FTY720 treatment can alleviate DENV-induced endothelial hyperpermeability. In functional assays, in both in vitro systems and in AG129 animal models, FTY720 treatment was found effective. Upon treatment, there was complete restoration of the monolayer integrity in DENV serotype 2-infected human microvascular endothelial cells (HMEC-1). At the molecular level, the treatment reversed activation of the S1P pathway. It significantly reduced the phosphorylation of the key molecules such as PTEN, RhoA, and VE-Cadherin; and also, the expression levels of S1PR2. In DENV2-infected AG129 mice treated with FTY720, there was significant improvement in weight gain, in overall clinical symptoms, and in survival. Whereas 100% of the DENV2-infected, untreated animals died by day-10 post-infection, 70% of the FTY720-treated animals were alive; and at the end of the 15-day post-infection observation period, 30% of them were still surviving. There was a significant reduction in the Evan's-blue dye permeability in the organs of FTY720-treated, DENV-2 infected animals; and also improvement in the hemogram, with complete restoration of thrombocytopenia and hepatic function. Our results show that the FDA-approved molecule Fingolimod (FTY720) is a promising therapeutic intervention in severe dengue.

Comparative Assessment of Reliability and Accuracy of Cone-Beam Computed Tomography (CBCT) Over Direct Surgical Measurement for Periodontal Bone Loss: A Prospective, Cross-Sectional Study.

INTRODUCTION: Assessing bone condition holds significant value in the diagnosis, treatment planning, and prognosing the periodontal disease; its importance is undeniable. The main aim of the present study was to evaluate the accuracy of alveolar bone measurements due to periodontal disease using cone-beam computed tomography (CBCT), by comparing with surgical measurements, considered as the gold standard. MATERIALS AND METHODS: A prospective cross-sectional study included a sample of 40 individuals diagnosed with chronic periodontitis who required periodontal surgery. A total of 202 sites were assessed for vertical and horizontal bone loss in the anterior (76 sites) and posterior (126 sites) teeth. Bone loss was measured using CBCT and a UNC 15 periodontal probe during the surgical intervention, and then compared. The statistical analysis involved employing a Student's t-test to compare measurements. Unpaired t-tests and correlation analyses were conducted using Pearson's correlation coefficient test. To establish statistical significance, a threshold of p<0.05 was considered appropriate. RESULTS: The statistical analysis carried out on the mean values of CBCT and direct surgical measurements for vertical bone loss demonstrated a significant difference (p<0.01). However, the values obtained for horizontal bone loss did not display statistical significance. A strong correlation of 0.94-0.99 existed between surgical and CBCT measurements. A statistically significant distinction was observed between the two methods in measuring bone loss at the distal and palatal sites of the anterior teeth. CONCLUSION: Both CBCT and direct surgical measurement exhibit comparable accuracy potential in assessing alveolar bone loss. CBCT provides an accessibility advantage by enhancing visual access to challenging sites during surgical interventions, including palatal and distal areas of the teeth.

Orthodontic-surgical management of severe skeletal class iii malocclusion: A case report.

Skeletal Class III malocclusion possess a difficult challenge to treat for clinicians. They are multifactorial and include genetic and environmental factors. Early intervention of Class III needs orthopedic correction, whereas, in adults, orthodontic camouflage can be done to treat mild cases while severe skeletal discrepancies demand orthognathic surgery along with orthodontic therapy. In this case report, a case of mandibular prognathism with Bilateral Sagittal Split Osteotomy (BSSO) setback was presented.

Oral administration of S-nitroso-L-glutathione (GSNO) provides anti-inflammatory and cytoprotective effects during ocular bacterial infections.

Bacterial endophthalmitis is a severe complication of eye surgeries that can lead to vision loss. Current treatment involves intravitreal antibiotic injections that control bacterial growth but not inflammation. To identify newer therapeutic targets to promote inflammation resolution in endophthalmitis, we recently employed an untargeted metabolomics approach. This led to the discovery that the levels of S-nitroso-L-glutathione (GSNO) were significantly reduced in an experimental murine Staphylococcus aureus (SA) endophthalmitis model. In this study, we tested the hypothesis whether GSNO supplementation via different routes (oral, intravitreal) provides protection during bacterial endophthalmitis. Our results show that prophylactic administration of GSNO via intravitreal injections ameliorated SA endophthalmitis. Therapeutically, oral administration of GSNO was found to be most effective in reducing intraocular inflammation and bacterial burden. Moreover, oral GSNO treatment synergized with intravitreal antibiotic injections in reducing the severity of endophthalmitis. Furthermore, in vitro experiments using cultured human retinal Muller glia and retinal pigment epithelial (RPE) cells showed that GSNO treatment reduced SA-induced inflammatory mediators and cell death. Notably, both in-vivo and ex-vivo data showed that GSNO strengthened the outer blood-retinal barrier during endophthalmitis. Collectively, our study demonstrates GSNO as a potential therapeutic agent for the treatment of intraocular infections due to its dual anti-inflammatory and cytoprotective properties.

Characterization of a recombinant factor IX molecule fused to coagulation factor XIII-B subunit.

INTRODUCTION AND AIM: Severe haemophilia B (HB) is characterized by spontaneous bleeding episodes, mostly into joints. Recurrent bleeds lead to progressive joint destruction called haemophilic arthropathy. The current concept of prophylaxis aims at maintaining the FIX level >3-5 IU/dL, which is effective at reducing the incidence of haemophilic arthropathy. Extended half-life FIX molecules make it easier to achieve these target trough levels compared to standard FIX concentrates. We previously reported that the fusion of a recombinant FIX (rFIX) to factor XIII-B (FXIIIB) subunit prolonged the half-life of the rFIX-LXa-FXIIIB fusion molecule in mice and rats 3.9- and 2.2-fold, respectively, compared with rFIX-WT. However, the mechanism behind the extended half-life was not known. MATERIALS AND METHODS: Mass spectrometry and ITC were used to study interactions of rFIX-LXa-FXIIIB with albumin. Pharmacokinetic analyses in fibrinogen-KO and FcRn-KO mice were performed to evaluate the effect of albumin and fibrinogen on in-vivo half-life of rFIX-LXa-FXIIIB. Finally saphenous vein bleeding model was used to assess in-vivo haemostatic activity of rFIX-LXa-FXIIIB. RESULTS AND CONCLUSION: We report here the key interactions that rFIX-LXa-FXIIIB may have in plasma are with fibrinogen and albumin which may mediate its prolonged half-life. In addition, using the saphenous vein bleeding model, we demonstrate that rFIX-FXIIIB elicits functional clot formation that is indistinguishable from that of rFIX-WT.

The ideal patient specific implant. Part II: An eight step checklist for maxillary class I, II Brown defects.

Patient specific implants (PSI) though considered the next frontier in Maxillofacial Reconstruction, the gold standard for Brown I, II maxillary defects still remains autogenous reconstruction. The authors in their previous papers have standardised the design of Patient Specific Implants for Brown I, II mandibular defects. In this paper they attempt to standardise the design of PSI for Brown I,II maxillary defects using a scientifically optimised design which has passed through a stringent set of parameters. They aim to address the complications like wound dehiscence, poor dimensional accuracy and unoptimised biomechanics due to lack of standardisation thus impeding it's widespread acceptance among the scientific community. This study presents an eight step checklist to be followed for designing of an ideal standardised patient specific implant and can serve as a go-to guide for the operating and designing team.

Genome-wide identification of bZIP transcription factor family in Artemisia annua, its transcriptional profiling and regulatory role in phenylpropanoid metabolism under different light conditions.

The basic leucine zipper (bZIP) protein transcription factors are known to modulate development, plant growth, metabolic response, and resistance to several biotic and abiotic stressors and have been widely studied in the model plant Arabidopsis thaliana. However, no comprehensive information about the bZIP transcription factor family in Artemisia annua has been explored to date. In this genome-wide study, we identified 61 bZIP TFs after removing false positives and incomplete sequences from Artemisia annua. Seven highly expressed homolog AabZIP TF genes under UV-B and differential light conditions in different tissues were identified from the publicly available microarray dataset as having their cis-regulatory elements involved in, flavonoids biosynthesis, seed-specific gene regulation, stress responses, and metabolic regulation. In-silico analysis and electrophoretic mobility shift assay (EMSA) confirmed the interaction of AabZIP19 TF over the AaPAL1 promoter in order to regulate the phenolics and flavonoid biosynthesis via the phenylpropanoid pathway. Further, RT-PCR analysis has been carried out to validate the transcript levels of selected AabZIP genes under white light, red light, blue light (45 min), and UV-B exposure (12 and 24 h). These genes have their highest expression levels under UV-B and blue light exposure, in contrast with white light. Therefore, the detection of ROS through staining confirms the accumulation of superoxide radicals and H2O2, and in addition to reducing ROS accumulation under UV-B and blue light irradiation, total phenols and flavonoids are significantly enhanced. This study laid the groundwork for deciphering the possible role of AabZIP TFs under different light stress-responsive conditions and in the regulation of secondary metabolism. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01338-0.

Biofunctionalization with Cissus quadrangularis phytobioactives accentuates Nano-Hydroxyapatite based ceramic Nano-Cement for Neo-Bone formation in critical sized bone defect.

Developing biofunctionalized ceramic bone substitutes with phytobioactives for their sustained delivery is highly desired to enhance the osteo-active potential of ceramic bone substitutes, reduce the systemic toxicity of synthetic drugs, and increase the bioavailability of phytobioactives. The present work highlights the local delivery of phytobioactives of Cissus quadrangularis (CQ) through nano-hydroxyapatite (nHAP) based ceramic nano-cement. The phytoconstituent profiling represented the optimized CQ fraction to be rich in osteogenic polyphenols and flavonoids like quercetin, resveratrol, and their glucosides. Further, CQ phytobioactives-based formulation was biocompatible, increased bone formation, calcium deposition, proliferation, and migration of cells with simultaneous alleviation of cellular oxidative stress. In the in vivo critical-sized bone defect model, enhanced formation of highly mineralized tissue (BV mm3) in CQ phytobioactives functionalized nano-cement (10.5 ± 2 mm3) were observed compared to the control group (6.5 ± 1.2 mm3). Moreover, the addition of CQ phytobioactives to the bone nano-cement increased the fractional bone volume (BV/TV%) to 21 ± 4.2% compared to 13.1 ± 2.5% in non-functionalized nano-cement. The results demonstrated nHAP-based nano-cement as a carrier for phytobioactives which could be a promising approach for neo-bone formation in different bone defect conditions.

Acceptance of on-site wastewater treatment and reuse in Bengaluru, India: The role of perceived costs, risks, and benefits.

In dealing with water pollution and freshwater scarcity, on-site treatment and reuse of domestic wastewater has shown to be a promising solution. To increase on-site wastewater treatment and reuse, some cities, among them Bengaluru in India, have mandated the installation and use of the necessary technology in certain building types. However, even with a mandate, a successful and sustainable implementation of the technology, including reliable operation, monitoring, and maintenance, depends on the acceptance (i.e. positive valuation) of the technology and its use by the (prospective) users. Literature on technology acceptance indicates perceived costs, risks, and benefits of the respective technology as key predictors of acceptance. Therefore, the present online study assessed this relationship for on-site systems in Bengaluru. The relation was analysed separately for mandated users of on-site systems (N = 103) and current non-users (i.e. potential prospective users, should the mandate be expanded; N = 232), as the perceptions might differ between the two groups, due to the personal experience with the technology among users. The results show that for mandated users and non-users, acceptance of on-site systems is explained by perceived benefits only, namely a positive image of users, environmental benefits, and, only for non-users, also financial benefits for the city. The findings suggest that interventions aimed at promoting on-site systems should include emphasis on the benefits of on-site systems. Whenever possible, interventions should be tailored to the target group's individual cost, risk, and benefit perception.