Dermoscopy of hypopigmented macules unveiling genetic diagnosis of tuberous sclerosis complex type 2 in an infant presenting with sacral chordoma.

A 2-month-old male with surgically resected sacral chordoma presented with multiple hypopigmented macules showing characteristic patchy, sharply demarcated areas of pigment network on dermoscopy. These dermoscopic findings were suggestive of the ash-leaf macules of tuberous sclerosis over other common hypopigmented macules in neonates. Chordomas presenting in early childhood in the sacral location have been reported as a rare manifestation of tuberous sclerosis complex. The combination of these findings led to a diagnosis of tuberous sclerosis, confirmed with the finding of a heterozygous TSC2 gene deletion; treatment with sirolimus resulted in regression of cardiac rhabdomyomas and hypopigmented macules.

Effect of PVP Molecular Weights on the Synthesis of Ultrasmall Cus Nanoflakes: Synthesis, Properties, and Potential Application for Phototheranostics.

Copper sulfide nanoparticles (CuS) hold tremendous potential for applications in photothermal therapy (PTT) and photoacoustic imaging (PAI). However, the conventional chemical coprecipitation method often leads to particle agglomeration issues. To overcome this challenge, we utilized polyvinylpyrrolidone (PVP) as a stabilizing agent, resulting in the synthesis of small PVP-CuS nanoparticles named PC10, PCK30, and PC40. Our study aimed to investigate how different molecular weights of PVP influence the nanoparticles' crystalline characteristics and essential properties, especially their photoacoustic and photothermal responses. While prior research on PVP-assisted CuS nanoparticles has been conducted, our study delves deeper into this area, providing insights into optical properties. Remarkably, all synthesized nanoparticles exhibited a crystalline structure, were smaller than 10 nm, and featured an absorbance peak at 1020 nm, indicating their robust photoacoustic and photothermal capabilities. Among these nanoparticles, PC10 emerged as the standout performer, displaying superior photoacoustic properties. Our photothermal experiments demonstrated significant temperature increases in all cases, with PC10 achieving an impressive efficiency of 51%. Moreover, cytotoxicity assays revealed the nanoparticles' compatibility with cells, coupled with an enhanced incidence of apoptosis compared to necrosis. These findings underscore the promising potential of PVP-stabilized CuS nanoparticles for advanced cancer theranostics.

Accelerating the understanding of Aspergillus terreus: Epidemiology, physiology, immunology and advances.

Aspergillus species encompass a variety of infections, ranging from invasive aspergillosis to allergic conditions, contingent upon the immune status of the host. In this spectrum, Aspergillus terreus stands out due to its emergence as a notable pathogen and its intrinsic resistance to amphotericin-B. The significance of Aspergillus-associated infections has witnessed a marked increase in the past few decades, particularly with the increasing number of immunocompromised individuals. The exploration of epidemiology, morphological transitions, immunopathology, and novel treatment approaches such as new antifungal drugs (PC945, olorofim) and combinational therapy using antifungal drugs and phytochemicals (Phytochemicals: quercetin, shikonin, artemisinin), also using immunotherapies to modulate immune response has resulted in better outcomes. Furthermore, in the context COVID-19 era and its aftermath, fungal infections have emerged as a substantial challenge for both immunocompromised and immunocompetent individuals. This is attributed to the use of immune-suppressing therapies during COVID-19 infections and the increase in transplant cases. Consequently, this review aims to provide an updated overview encompassing the epidemiology, germination events, immunopathology, and novel drug treatment strategies against Aspergillus terreus-associated infections.

Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review.

Traditional medication and alternative therapies have long been used to treat breast cancer. One of the main problems with current treatments is that there is an increase in drug resistance in the cancer cells owing to genetic differences such as mutational changes, epigenetic changes and miRNA (microRNA) alterations such as miR-1246, miR-298, miR-27b and miR-33a, along with epigenetic modifications, such as Histone3 acetylation and CCCTC-Binding Factor (CTCF) hypermethylation for drug resistance in breast cancer cell lines. Certain forms of conventional drug resistance have been linked to genetic changes in genes such as ABCB1, AKT, S100A8/A9, TAGLN2 and NPM. This review aims to explore the current approaches to counter breast cancer, the action mechanism, along with novel therapeutic methods endowing potential drug resistance. The investigation of novel therapeutic approaches sheds light on the phenomenon of drug resistance including genetic variations that impact distinct forms of oestrogen receptor (ER) cancer, genetic changes, epigenetics-reported resistance and their identification in patients. Long-term effective therapy for breast cancer includes selective oestrogen receptor modulators, selective oestrogen receptor degraders and genetic variations, such as mutations in nuclear genes, epigenetic modifications and miRNA alterations in target proteins. Novel research addressing combinational therapies including maytansine, photodynamic therapy, guajadiol, talazoparib, COX2 inhibitors and miRNA 1246 inhibitors have been developed to improve patient survival rates.

Short-term, nonsurgical periodontal therapy boosts interleukin-12 levels and reduces oral cancer risk.

BACKGROUND: Cytokines, including interleukin-12 (IL-12), are proteins that regulate cell survival, proliferation, differentiation, and function. IL-12 is a heterodimeric proinflammatory cytokine. It possesses tumoricidal properties and promotes M1 macrophage polarization and IFN-γ production by T helper (Th1) cells, which in turn stimulates the antitumor cytotoxic cluster of eight positive (CD8+) and natural killer cells, therefore activating an effector immune response against tumor cells. MATERIALS AND METHODS: Herein, the IL-2 levels of 60 patients with generalized chronic periodontitis (GCP) were assessed. Plaque index, gingival index, pocket probing depth, bleeding on probing percentage (BOP %), and clinical attachment loss were the clinical indicators reported. RESULTS: Patients with GCP in the pretreatment group had substantially lower mean IL-12 levels than those in the post-treatment group. Short-term, nonsurgical treatment (NST) considerably improved periodontal indices and increased IL-12 levels, thereby reducing oral cancer risk. CONCLUSION: NST is a cost-effective and accessible cancer prevention procedure for general dentists.

Increased endothelial sclerostin caused by elevated DSCAM mediates multiple trisomy 21 phenotypes.

Trisomy 21 (T21), a recurrent aneuploidy occurring in 1:800 births, predisposes to congenital heart disease (CHD) and multiple extracardiac phenotypes. Despite a definitive genetic etiology, the mechanisms by which T21 perturbs development and homeostasis remain poorly understood. We compared the transcriptome of CHD tissues from 49 patients with T21 and 226 with euploid CHD (eCHD). We resolved cell lineages that misexpressed T21 transcripts by cardiac single-nucleus RNA sequencing and RNA in situ hybridization. Compared with eCHD samples, T21 samples had increased chr21 gene expression; 11-fold-greater levels (P = 1.2 × 10-8) of SOST (chr17), encoding the Wnt inhibitor sclerostin; and 1.4-fold-higher levels (P = 8.7 × 10-8) of the SOST transcriptional activator ZNF467 (chr7). Euploid and T21 cardiac endothelial cells coexpressed SOST and ZNF467; however, T21 endothelial cells expressed 6.9-fold more SOST than euploid endothelial cells (P = 2.7 × 10-27). Wnt pathway genes were downregulated in T21 endothelial cells. Expression of DSCAM, residing within the chr21 CHD critical region, correlated with SOST (P = 1.9 × 10-5) and ZNF467 (P = 2.9 × 10-4). Deletion of DSCAM from T21 endothelial cells derived from human induced pluripotent stem cells diminished sclerostin secretion. As Wnt signaling is critical for atrioventricular canal formation, bone health, and pulmonary vascular homeostasis, we concluded that T21-mediated increased sclerostin levels would inappropriately inhibit Wnt activities and promote Down syndrome phenotypes. These findings imply therapeutic potential for anti-sclerostin antibodies in T21.

Monkeypox (Mpox): Evolution of Transmission and Comprehensive Review.

The human monkeypox (mpox) virus is an orthopox virus that can be transmitted to humans. Though the disease has been endemic in Africa, the recent mpox outbreak since May 2022. We attempted to examine differences between the endemic form of mpox and the current outbreak. Review of electronic medical database with relevant keywords. The current outbreak of mpox has disproportionately impacted the gay, bisexual and other men who have sex with men (MSM) community. This is also the first time that widespread semen testing has turned up evidence of mpox viral deoxyribonucleic acid (DNA). Cases in the present outbreak are more likely to affect adults, involve the genitalia, and have no prodrome. Close diagnostic differentials include varicella and hand-foot-mouth disease. The disease is usually self-limiting; though secondary infections, anorectal pain, pharyngitis, ocular lesions and rarely, renal injury and myocarditis may occur. This review focuses primarily on the novel clinical characteristics and emerging sexual transmission route of the mpox virus, which, although unconfirmed, appears extremely likely as the route of spread. Dermatologists have an important role in this health emergency, as early diagnosis can cause a significant reduction in disease transmission.

Transcutaneous electrical stimulation of auricular branch of the vagus nerve effectively and rapidly modulates the EEG patterns in patients with possible electrographic status epilepticus.

BACKGROUND: Invasive vagal nerve stimulation (iVNS) is a known treatment approach for patients with refractory epilepsy. Transcutaneous auricular vagus nerve stimulation (tVNS) was developed to overcome the side effects and surgical complications of iVNS. tVNS is proven beneficial in refractory epilepsy. The effectiveness of tVNS, however, has never been studied in patients with Status Epilepticus. In this study, we explored the effect of tVNS in three patients with possible electrographic status epilepticus. OBJECTIVES: To compare the EEG pattern before, during and after tVNS in three patients with possible electrographic status epilepticus. METHODS: Three consecutive patients with possible electrographic status epilepticus were included after due consenting process. In addition to the standard care, tVNS was applied on the left ear over the cymba concha in two sessions, 6 h apart, with each session for 45 min. Continuous EEG monitoring was performed as standard of care and the findings before, during and after tVNS were documented. RESULTS: The duration of status epilepticus at the time of inclusion of Patients 1, 2, and 3 was 6 weeks, 7 days, and 5 days respectively. All were in coma and on multiple antiseizure medications. Patient 1 and 3 were on anesthetic infusions. Before stimulation, one patient had burst suppression pattern and two had generalized periodic discharges at 1 Hz frequency. We observed a significant reduction/resolution of ongoing EEG patterns in all three patients during the stimulation. The abnormal patterns re-emerged approximately 20 min post cessation of tVNS. No stimulation-related side effects were detected. There was no change in clinical status, but all three patients had severe underlying conditions. SIGNIFICANCE: Transcutaneous auricular Vagus Nerve Stimulation (tVNS) is a potential noninvasive adjuvant therapy that can modulate EEG patterns in patients with Status epilepticus. Larger studies in early SE are needed to assess its clinical benefits.

Utility of 18F-FDG PET/CT in Assessment of Disease Extent and Response to Treatment in Xanthoma Disseminatum.

The clinical utility of 18F-FDG PET/CT is being increasingly recognized in histiocytic disorders. We report the case of a 23-y-old woman who presented with slowly progressive, yellowish-brown papules, plaques, and nodules over her face and flexures. Besides the multiple cutaneous lesions, lesions of the brain, stomach, gallbladder, and marrow were additionally revealed by baseline 18F-FDG PET/CT. Skin biopsy and the overall clinical picture were consistent with xanthoma disseminatum. Subsequent PET/CT after cladribine therapy revealed a decrease in the extent and metabolic activity of most lesions, suggestive of a favorable response. This case report highlights the potential role of 18F-FDG PET/CT in the accurate assessment of disease extent and posttreatment response in rare histiocytic disorders.

Procedural dermatology and its unmet need.

Procedural dermatology includes invasive conventional dermatologic surgeries which involve significant use of knife and suture, minimally invasive procedures and device-based procedures. Device-based procedures are the easiest to learn and are less prone to human errors due to automation but can lead to monotony, while conventional surgeries require significant skill, craftsmanship and interest. There has been a recent shift in the approach to procedural dermatology as a therapeutic option with complementary and combination models replacing the conventional hierarchical model in which procedures were last in the step-ladder approach. The demand for both conventional dermatologic surgeries and minimally invasive cosmetic procedures is increasing. Unfortunately, this demand has not been met with adequate supply. Consequently, the number of trained professionals with expertise in these procedures is very limited; they are far outnumbered by unqualified practitioners. A limited number of dermatologic surgeons practicing conventional surgeries has resulted in huge waiting lists for vitiligo surgeries, inappropriate excisions for skin cancers and poor cosmetic outcomes of excisions without proper knowledge of flaps and grafts. Increasingly procedures are being performed by inadequately trained personnel, resulting in complications. There is also an absence of good quality research on the subject of procedural dermatology, which has resulted in a lack of standardisation of various procedures and knowledge about the efficacy of various drug-procedure and procedure-procedure combinations. An increasing variety of gimmicky but costly procedures are being offered to the public without much evidence of efficacy. Individual institutional and broad policy directives are needed to address these issues. Special emphasis is required on formal hands-on procedural dermatology training during residency and beyond it.

Current understanding of frictional dermatoses: A review.

Human skin is continually exposed to internal and external forces, dynamic as well as static. The skin is normally flexible and can resist mechanical trauma due to friction, pressure, vibration, suction and laceration to a considerable degree. However, an excess of these forces can abnormally affect the structure and function of the skin, setting the stage for the development of a skin disorder. Repetitive trauma can cause lichenification, hyperpigmentation, erythema, scaling, fissuring, blisters, ulceration and chronic alterations. Frictional dermatoses is an under-recognised entity with no clear-cut definition and encompasses a variety of terms such as frictional dermatitis, frictional melanosis, frictional pigmentary dermatoses and certain other named entities, many of which are confusing. The authors propose to define frictional dermatoses as 'a group of disorders caused by repetitive trauma to the skin as a result of friction of varied aetiology which can have a wide range of cutaneous manifestations depending on the type of insult.' The exact prevalence of frictional dermatoses as a separate entity is unknown. Authors who conducted this review include a group of dermatologists and post graduate students from various institutions. Literature was reviewed through PubMed, Medscape, Medline, ResearchGate and Google Scholar using the terms 'frictional dermatitis,' 'friction and skin,' 'dermatoses and culture,' 'clothing dermatitis,' 'friction melanosis,' 'PPE induced dermatoses in COVID-19 era,' etc. A total of 122 articles were reviewed and 100 articles among them were shortlisted and included in the study, after removing duplications. The review was followed up with further deliberation which resulted in the formulation of a new definition and classification of frictional dermatoses taking into account the morphology, histopathological characteristics, anatomical region affected and the major predisposing factors. The rising incidence of mechanical dermatoses in the COVID-19 era was also emphasised.

Characterizing Viscoelastic Polyvinyl Alcohol Phantoms for Ultrasound Elastography.

Ultrasound phantoms mimic the acoustic and mechanical properties of native tissues. Polyvinyl alcohol (PVA) phantoms are used extensively as models for validating ultrasound elastography approaches. However, the viscous properties of PVA phantoms have not been investigated adequately. Glycerol is a viscous liquid that has been reported to increase the speed of sound of phantoms. This study aims to assess the acoustic and viscoelastic properties of PVA phantoms and PVA mixed with glycerol at varying concentrations. The phantoms were fabricated with 10% w/v PVA in water with varying concentrations of glycerol (10%, 15% and 20% v/v) and 2% w/v silicon carbide particles as acoustic scatterers. The phantoms were subjected to either one, two, or three 24-h freeze-thaw cycles. The longitudinal sound speeds of all PVA phantoms were measured, and ranged from 1529 to 1660 m/s. Attenuation spectroscopy was performed in the range of 5 to 20 MHz. The measured attenuation followed a power-law relationship with frequency, wherein the power-law fit constants and exponents ranged from 0.02 to 0.1 dB/cm/MHzn and from 1.6 to 1.9, respectively. These results were in agreement with previous reports for soft tissues. Viscoelasticity of PVA phantoms was assessed using rheometry. The estimated values of shear modulus and viscosity using the Kelvin-Voigt and Kelvin-Voigt fractional derivative models were within the range of previously-reported tissue-mimicking phantoms and soft tissues. The number of freeze-thaw cycles were shown to alter the viscosity of PVA phantoms, even in the absence of glycerol. Scanning electron microscopy images of PVA phantoms without glycerol showed a porous hydrogel network, in contrast to those of PVA-glycerol phantoms with non-porous structure. Phantoms fabricated in this study possess tunable acoustic and viscoelastic properties within the range reported for healthy and diseased soft tissues. This study demonstrates that PVA phantoms can be manufactured with glycerol for applications in ultrasound elastography.

Molecular diagnosis of Tuberculous meningitis: sdaA-based multi-targeted LAMP and GeneXpert Ultra.

SETTING: Nucleic acid amplification techniques like GeneXpert and GeneXpert Ultra (Xpert Ultra), the first-line tests for diagnosing Tuberculous meningitis (TBM), are expensive and depend on sophisticated equipment. OBJECTIVE: The diagnostic potential of multitargeted loop-mediated isothermal assay (MLAMP), a low-cost simple test using novel gene combination, was evaluated for TBM. DESIGN: 300 CSF specimen (200 TBM patients, 100 controls) processed between January 2017 and December 2021 were subjected to MLAMP (using sdaA, IS1081 and IS6110 gene targets), sdaA PCR and Xpert Ultra. The performance was evaluated against uniform case definition as per Marais criteria, and against culture. RESULTS: Uniform case definition classified 50 as definite TBM and 150 as probable or definite TBM. Against this uniform case definition, the sensitivity and specificity of MLAMP was 88% and 100%, respectively. The sensitivity was 96% against culture-positive cases and 85.3% against culture-negative cases. The sensitivity of sdaA-LAMP, IS1081-LAMP, IS6110-LAMP, Xpert Ultra and sdaA-PCR was 82.5%, 80.5%, 85.3%, 67% and 71%, respectively against uniform case definition. sdaA-LAMP detected additional two cases and IS1081-LAMP detected nine. 11 of 134 (8.2%) cases were reported rifampicin resistant by Xpert Ultra. CONCLUSION: MLAMP, incorporating sdaA and IS1081, is a cheap, easy and accurate first-line diagnostic test for TBM.

The effect of non-surgical periodontal therapy on salivary IL-6 levels in patients with moderate to severe generalized chronic periodontitis.

BACKGROUND: Gene regulation of IL-6 is characterized by the presence of inflammatory cytokines, bacterial products, viral infection, and activation of the diacylglycerol-, cyclic AMP-, or Ca + + -activated signal transduction pathways. AIM: Scaling and root planning (SRP), a non-surgical periodontal therapy, was studied in connection to several clinical parameters for its effect on salivary IL-6 levels in patients with generalized chronic periodontitis. METHODS: For this study, a total of 60 GCP patients were included. Plaque index (PI), gingival index (GI), pocket probing depth (PPD), bleeding on probing percentage (BOP%), and clinical attachment loss were among the clinical indicators covered (CAL). RESULTS: Following SRP, mean IL-6 levels in patients with GCP were significantly higher in the pre-treatment group (2.93 5.17 pg/ml; p 0.05) than in the posttreatment group (5.78 8.26 pg/ml; baseline). Pre- and post-treatment IL-6 levels for PI (pre), BOP percent (pre/post), GI (post), and PPD were found to be positively correlated (post). In patients with GCP, the study showed a statistically significant correlation between periodontal metrics and salivary IL-6. CONCLUSIONS: Changes in periodontal indices and IL-6 levels that are statistically significant over time indicate that non-surgical treatment is effective, and IL-6 can be regarded as a potent disease activity marker.

Role of Tunneling Nanotubes in Viral Infection, Neurodegenerative Disease, and Cancer.

The network of tunneling nanotubes (TNTs) represents the filamentous (F)-actin rich tubular structure which is connected to the cytoplasm of the adjacent and or distant cells to mediate efficient cell-to-cell communication. They are long cytoplasmic bridges with an extraordinary ability to perform diverse array of function ranging from maintaining cellular physiology and cell survival to promoting immune surveillance. Ironically, TNTs are now widely documented to promote the spread of various pathogens including viruses either during early or late phase of their lifecycle. In addition, TNTs have also been associated with multiple pathologies in a complex multicellular environment. While the recent work from multiple laboratories has elucidated the role of TNTs in cellular communication and maintenance of homeostasis, this review focuses on their exploitation by the diverse group of viruses such as retroviruses, herpesviruses, influenza A, human metapneumovirus and SARS CoV-2 to promote viral entry, virus trafficking and cell-to-cell spread. The later process may aggravate disease severity and the associated complications due to widespread dissemination of the viruses to multiple organ system as observed in current coronavirus disease 2019 (COVID-19) patients. In addition, the TNT-mediated intracellular spread can be protective to the viruses from the circulating immune surveillance and possible neutralization activity present in the extracellular matrix. This review further highlights the relevance of TNTs in ocular and cardiac tissues including neurodegenerative diseases, chemotherapeutic resistance, and cancer pathogenesis. Taken together, we suggest that effective therapies should consider precise targeting of TNTs in several diseases including virus infections.