Dual Endothelin Antagonism with Aprocitentan as a Novel Therapeutic Approach for Resistant Hypertension.

PURPOSE OF REVIEW: Resistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses is associated with a substantially increased risk of cardiovascular and renal events. Despite targeting relevant pathophysiological pathways contributing to elevated blood pressure, approximately 10-15% of hypertensive patients remain above recommended blood pressure targets. Further optimization of blood pressure control is particularly challenging in patient populations who frequently present with RH such as elderly and patients with chronic kidney disease, due to the unfavorable safety profile of the recommended fourth-line therapy with mineralocorticoid receptor antagonists. This review explores the potential role of endothelin antagonists as an alternative fourth-line therapy. RECENT FINDINGS: Despite the well-described role of the endothelin pathway in the pathogenesis of hypertension, it is currently not targeted therapeutically. Recently however, main outcome data from the PRECISION study, a randomized placebo-controlled phase 3 trial, in patients with RH on guideline-recommended standardized single-pill background therapy convincingly demonstrated the safety and blood pressure-lowering efficacy of the dual endothelin antagonist Aprocitentan. Findings from the phase 3 PRECISION study could signify a turning point in the utilization of endothelin receptor antagonists as a standard treatment for patients with RH.

Interaction between sodium-glucose co-transporter 2 and the sympathetic nervous system.

PURPOSE OF REVIEW: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have taken centre stage in research and therapeutic efforts to modulate hard clinical outcomes in patients with heightened cardiovascular and renal risk profiles. Sympathetic nervous system (SNS) activation is a prominent feature across several cardiovascular and renal disease states. This review reflects on the remarkable clinical impact of SGLT2 inhibitors on cardiorenal outcomes, and navigates the evidence for a proposed clinically relevant interaction between SGLT2 and the SNS. RECENT FINDINGS: SGLT2 inhibitors exert several pleiotropic effects beyond glucose-lowering. These include, but are not limited to, diuresis and natriuresis, blood pressure lowering, reduction in inflammation and oxidative stress, stimulation of erythropoiesis, and improvement in cardiac energetics. Treatment with SGLT2 inhibitors is associated with significant improvement in cardiorenal outcomes irrespective of diabetes status. In addition, evidence from preclinical studies points to a strong signal of a bidirectional temporal association between SGLT2 inhibition and reduction in SNS activation. SUMMARY: Ongoing preclinical and clinical trials aimed at unravelling the proposed interaction between SGLT and SNS will enhance our understanding of their individual and/or collective contributions to cardiovascular disease progression and guide future targeted therapeutic interventions.

Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition.

PURPOSE OF REVIEW: The moderate glucose-lowering effect of sodium glucose co-transporter 2 (SGLT2) inhibitors is unlikely to explain SGLT2 inhibitor-mediated beneficial outcomes, and unravelling the underlying mechanisms is a high priority in the research community. Given the dominant pathophysiologic role of the sympathetic nervous system activation in conditions such as hypertension and perturbed glucose homeostasis, it is pertinent to postulate that SGLT2 inhibitors may exert their beneficial effects at least in part via sympathetic inhibition. RECENT FINDINGS: SGLT2 inhibitors have shown enormous potential to improve cardiovascular outcomes in patients with type 2 diabetes, and their therapeutic potential is currently being investigated in a range of associated comorbidities such as heart failure and chronic kidney disease. Indeed, recent experimental data in relevant animal models highlight a bidirectional interaction between sympathetic nervous system activation and SGLT2 expression, and this facilitates several of the features associated with SGLT2 inhibition observed in clinical trials including improved glucose metabolism, weight loss, increased diuresis, and lowering of blood pressure. Currently available data highlight the various levels of interaction between the sympathetic nervous system and SGLT2 expression and explores the potential for SGLT2 inhibition as a therapeutic strategy in conditions commonly characterised by sympathetic activation.

Cough as a clinical manifestation of large vessel vasculitis.

Cough is not a widely recognised symptom of large vessel vasculitides. If not promptly diagnosed and treated, large vessel vasculitis can have serious clinical consequences. We present the case of a 76-year-old man who presented with a subacute history of persistent dry cough, was found to have extensive aortitis on imaging, and experienced rapid resolution of symptoms with immunosuppression.

Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers.

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme's association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients.

The impact of COVID-19 pandemic on training and mental health of residents: a cross-sectional study.

BACKGROUND: Residency programs have been impacted by the Coronavirus disease 2019 (COVID-19) pandemic. In this study we aim to investigate and evaluate the impact of the pandemic on residents as well as residency training programs. METHODS: This was a cross-sectional study including a survey of 43 questions prepared on Google forms and electronically distributed among a convenience sample of residents training at a tertiary center in North Jordan during the COVID-19 pandemic. Data were collected in the period between October 30th and November 8th of 2020. The survey included questions that addressed the impact of the pandemic on residents' health as well as training programs. The study participants included residents in training at KAUH in 2020 and were stratified according to the type of residency program (surgical residents (SRs) and non-surgical residents (NSRs)). Statistical methods included descriptive analysis, Chi-square or Fisher's exact test, Mann Whitney U test, and Cramer's V and r statistics as measures of effect sizes. RESULTS: Of all 430 residents, 255 (59%) responded to the survey. A total of 17 (7%) of residents reported being infected with COVID-19 and a significant difference was reported between SRs and NSRs (10% vs 4%, V = .124 "small effect" (95% CI; .017-.229), p = 0.048). Approximately, 106 (42%) reported a decrease in the number of staff working at the clinic and 164 (64%) reported limited access to personal protective equipment during the pandemic. On a 4-point Likert scale for the feeling of anxiety, the median was 2 (2-3 IQR) in the NSRs group, vs 2 (1-2 IQR) in the SRs groups, with the NSRs being more likely to feel anxious (r = 0.13 "small effect" (95% CI; 0.007-0.249), p = .044). Similarly, the proportion of residents who reported feeling anxious about an inadequacy of protective equipment in the work area was significantly greater in the NSRs group (90.3% vs 75.2%; V = .201 "small effect" (95% CI; .078-.313), p = .001), as well as the proportion of residents who reported feeling increased stress and anxiety between colleagues being also significantly higher in the NSRs group (88.1% vs 76%; V = .158 "small effect" (95% CI; .032-.279), p = .012). CONCLUSION: The burden of the ongoing pandemic on the mental health status of residents is very alarming and so providing residents with psychological counseling and support is needed. Also, critical implications on the flow of residency training programs have been noticed. This necessitates adapting and adopting smart educational techniques to compensate for such limitations.

Interventional Approaches for Loin Pain Hematuria Syndrome and Kidney-Related Pain Syndromes.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) frequently presents with severe chronic pain that poses a clinical challenge. Current treatment approaches are mostly empirical and include a wide range of therapeutic strategies such as physical therapy, local and systemic analgesia, interventional and surgical approaches usually flanked by psycho-behavioral therapy, and other strategies. LPHS often impacts negatively on quality of life particularly in patients who are refractory to treatment. RECENT FINDINGS: With recent advances in catheter-based treatment approaches and better understanding of the pathophysiology of LPHS, intraluminal renal denervation (RDN) has been proposed as a valuable treatment option for kidney-related pain syndromes. The present review provides a brief overview of the clinical challenges associated with LPHS, highlights recent insights into its underlying mechanisms, and summarizes currently available data on the use of RDN in the context of LPHS and kidney-related pain syndromes. Renal denervation via various approaches including surgical and catheter-based techniques has shown promise in alleviating kidney-related pain syndromes. Randomized controlled trials are now required to better define its role in the management of these conditions.

In vitro anti-inflammatory potential of phloretin microemulsion as a new formulation for prospective treatment of vaginitis.

Phloretin is a promising polyphenolic compound known for its anti-inflammatory properties, but its poor solubility and low bioavailability hinder its clinical applicability. Till current date, its potential in the treatment of vaginitis has not been explored, and only very few papers reported its formulation as nanoparticles to overcome its pharmaceutical challenges. Therefore, in the current study, phloretin was formulated in microemulsion of 11 nm size, and its in vitro anti-inflammatory properties were explored using histamine and IL-6 release inhibition assays, protease inhibition assay, and membrane stabilization potential. The anti-inflammatory properties of phloretin microemulsion were compared to the drug phloretin, and the reference standard non-steroidal anti-inflammatory drugs (NSAIDs). Results proved that both phloretin and phloretin microemulsion significantly inhibited the release of the inflammatory mediators histamine and IL-6, inhibited protease action, and exhibited membrane stabilization potential. Phloretin microemulsion exhibited comparable anti-inflammatory properties to the NSAIDs diclofenac and indomethacin, and, hence, it can be delineated as a promising therapeutic tool in topical treatment of vaginal inflammation.

New Molecules for Treating Resistant Hypertension: a Clinical Perspective.

PURPOSE OF REVIEW: To review the findings of trials evaluating pharmacological treatment approaches for hypertension in general, and resistant hypertension (RH) in particular, and propose future research and clinical directions. RECENT FINDINGS: RH is defined as blood pressure (BP) that remains above target levels despite adherence to at least three antihypertensive medications, including a diuretic. Thus far, clinical trials of pharmacological approaches in RH have focused on older molecules, with spironolactone being demonstrated as the most efficacious fourth-line agent. However, the use of spironolactone in clinical practice is hampered by its side effect profile and the risk of hyperkalaemia in important RH subgroups, such as patients with moderate-severe chronic kidney disease (CKD). Clinical trials of new molecules targeting both well-established and more recently elucidated pathophysiologic mechanisms of hypertension offer a multitude of potential treatment avenues that warrant further evaluation in the context of RH. These include selective mineralocorticoid receptor antagonists (MRAs), aldosterone synthase inhibitors (ASIs), activators of the counterregulatory renin-angiotensin-system (RAS), vaccines, neprilysin inhibitors alone and in combined formulations, natriuretic peptide receptor agonists A (NPRA-A) agonists, vasoactive intestinal peptide (VIP) agonists, centrally acting aminopeptidase A (APA|) inhibitors, antimicrobial suppression of central sympathetic outflow (minocycline), dopamine ß-hydroxylase (DßH) inhibitors and Na+/H+ Exchanger 3 (NHE3) inhibitors. There is a paucity of data from trials evaluating newer molecules for the treatment of RH. Emergent novel molecules for non-resistant forms of hypertension heighten the prospects of identifying new, effective and well-tolerated pharmacological approaches to RH. There is a glaring need to undertake RH-focused trials evaluating their efficacy and clinical applicability.

Lactation ketoacidosis: an easily missed diagnosis.

Ketoacidosis is uncommon in non-diabetic women, but occurs in the postpartum period as a rare complication of continuing to breastfeed during periods of acute illness. We report a case of a lactating woman who presented with severe symptomatic ketoacidosis in the early postpartum period. We also review the pathophysiology and management of lactation ketoacidosis.

Resistant Hypertension: Which Agent?

Resistant hypertension is commonly defined as office blood pressure above recommended target despite the use of optimal doses of at least three antihypertensive drugs including a diuretic. Australian guidelines recommend combination of blockers of the renin-angiotensin system, either ACE inhibitors or angiotensin receptor blockers, with calcium channel blockers and diuretics as the preferred triple therapy. A substantial proportion of hypertensive patients will require additional pharmacotherapy to achieve or get close to target blood pressure levels. Here we briefly review the evidence currently available to provide guidance on the most appropriate choice for additional antihypertensive pharmacotherapy and touch on interventional approaches that may be considered in some patients.

The Role of Sympatho-Inhibition in Combination Treatment of Obesity-Related Hypertension.

Obesity-related hypertension is commonly characterized by increased sympathetic nerve activity and is therefore acknowledged as a predominantly neurogenic form of hypertension. The sustained sympatho-excitation not only contributes to the rise in blood pressure but also elicits a vicious cycle which facilitates further weight gain and progression of associated co-morbidities. While weight loss and exercise remain at the forefront of therapy for obesity and obesity-related hypertension, the difficulties in achieving and maintaining long-term weight loss with lifestyle measures and the variable blood pressure response to weight loss often necessitate prescription of antihypertensive drug therapy. Remarkably, there are no specific recommendations for pharmacologic treatment for obese patients with arterial hypertension in any of the current guidelines and general principles of antihypertensive treatment are applied. The use of ß-blockers and diuretics is commonly discouraged as first- or second-line therapy due to their unfavorable metabolic effects. This review explores evolving therapeutic strategies which based on their interference with pathophysiologic mechanism relevant in the context of obesity may guide optimized treatment of obesity-related hypertension.

Radiation hybrid maps of the D-genome of Aegilops tauschii and their application in sequence assembly of large and complex plant genomes.

BACKGROUND: The large and complex genome of bread wheat (Triticum aestivum L., ~17 Gb) requires high resolution genome maps with saturated marker scaffolds to anchor and orient BAC contigs/ sequence scaffolds for whole genome assembly. Radiation hybrid (RH) mapping has proven to be an excellent tool for the development of such maps for it offers much higher and more uniform marker resolution across the length of the chromosome compared to genetic mapping and does not require marker polymorphism per se, as it is based on presence (retention) vs. absence (deletion) marker assay. METHODS: In this study, a 178 line RH panel was genotyped with SSRs and DArT markers to develop the first high resolution RH maps of the entire D-genome of Ae. tauschii accession AL8/78. To confirm map order accuracy, the AL8/78-RH maps were compared with:1) a DArT consensus genetic map constructed using more than 100 bi-parental populations, 2) a RH map of the D-genome of reference hexaploid wheat 'Chinese Spring', and 3) two SNP-based genetic maps, one with anchored D-genome BAC contigs and another with anchored D-genome sequence scaffolds. Using marker sequences, the RH maps were also anchored with a BAC contig based physical map and draft sequence of the D-genome of Ae. tauschii. RESULTS: A total of 609 markers were mapped to 503 unique positions on the seven D-genome chromosomes, with a total map length of 14,706.7 cR. The average distance between any two marker loci was 29.2 cR which corresponds to 2.1 cM or 9.8 Mb. The average mapping resolution across the D-genome was estimated to be 0.34 Mb (Mb/cR) or 0.07 cM (cM/cR). The RH maps showed almost perfect agreement with several published maps with regard to chromosome assignments of markers. The mean rank correlations between the position of markers on AL8/78 maps and the four published maps, ranged from 0.75 to 0.92, suggesting a good agreement in marker order. With 609 mapped markers, a total of 2481 deletions for the whole D-genome were detected with an average deletion size of 42.0 Mb. A total of 520 markers were anchored to 216 Ae. tauschii sequence scaffolds, 116 of which were not anchored earlier to the D-genome. CONCLUSION: This study reports the development of first high resolution RH maps for the D-genome of Ae. tauschii accession AL8/78, which were then used for the anchoring of unassigned sequence scaffolds. This study demonstrates how RH mapping, which offered high and uniform resolution across the length of the chromosome, can facilitate the complete sequence assembly of the large and complex plant genomes.

Recent developments in the management of resistant hypertension: focus on endothelin receptor antagonists.

Resistant hypertension is characterized by the inability of guideline-recommended triple combination therapy to control blood pressure (BP) to target. It is associated with a significantly increased risk of adverse outcomes. Despite abundant preclinical evidence supporting the critical role of the endothelin pathway in resistant hypertension (RH), clinical implementation of endothelin antagonists for the treatment of hypertension was hindered by various factors. Recently, the novel dual endothelin-receptor antagonist aprocitentan was tested in individuals with resistant hypertension in the PRECISION trial and provided compelling evidence supporting both short and longer-term safety and clinically meaningful and sustained BP lowering efficacy. These findings resulted in the recent regulatory approval of aprocitentan by the FDA. Aprocitentan may be a particularly useful antihypertensive option for individuals with advanced age, chronic kidney disease, and albuminuria.

What is this article about? Elevated blood pressure that remains uncontrolled despite recommended drug treatment with at least three established medications including a diuretic, also known as resistant hypertension, is a worldwide health concern and leaves many patients at high risk for adverse cardiovascular consequences such as heart attacks, strokes, and chronic kidney disease. While past research suggested the potential utility of endothelin receptor antagonists in managing hypertension, their efficacy remained unconfirmed until recently.What are the results of the PRECISION study? The PRECISION study examined the safety and efficacy of a novel dual endothelin receptor antagonist aprocitentan in individuals with resistant hypertension. The trial demonstrated that aprocitentan effectively lowered blood pressure both with short- and long-term administration and that it had a favorable safety profile.What do the results of the PRECISION study mean? As a direct consequence of the trial findings, aprocitentan is now approved by the US FDA for the treatment of uncontrolled blood pressure. This drug may prove particularly useful in individuals with clinical features known to render elevated blood pressure more difficult to control such as advanced age, chronic kidney disease, and increased levels of protein in their urine.

Taming resistant hypertension: The promise of novel pharmacologic approaches and renal denervation.

Resistant hypertension is associated with an exceedingly high cardiovascular risk and there remains an unmet therapeutic need driven by pathophysiologic pathways unaddressed by guideline-recommended therapy. While spironolactone is widely considered as the preferable fourth-line drug, its broad application is limited by its side effect profile, especially off-target steroid receptor-mediated effects and hyperkalaemia in at-risk subpopulations. Recent landmark trials have reported promising safety and efficacy results for a number of novel compounds targeting relevant pathophysiologic pathways that remain unopposed by contemporary drugs. These include the dual endothelin receptor antagonist, aprocitentan, the aldosterone synthase inhibitor, baxdrostat and the nonsteroidal mineralocorticoid receptor antagonist finerenone. Furthermore, the evidence base for consideration of catheter-based renal denervation as a safe and effective adjunct therapeutic approach across the clinical spectrum of hypertension has been further substantiated. This review will summarise the recently published evidence on novel antihypertensive drugs and renal denervation in the context of resistant hypertension.

Atypical Vaginal Aggressive Angiomyxoma in a Virgin: A Case Report from South Jordan.

Aggressive angiomyxoma is a locally invasive, rarely diagnosed mesenchymal tumor that predominantly affects the perineal region of women in their reproductive years. It is typically found in areas such as the vagina, vulva, and other pelvic soft tissues, but its presentation can be highly variable. We describe a particularly unique case of aggressive angiomyxoma, presenting in an atypical manner within the vaginal region of a 31-year-old virgin woman. This case is noteworthy for the unusual growth pattern of the angiomyxoma-located strictly within the vaginal epithelium, showing no signs of invasion into surrounding tissues, which is not typical of the aggressive nature of this type of tumor. The patient presented with a mass that protruded through the hymen, an uncommon presentation that led to initial speculation about the nature of the mass. The definitive diagnosis of aggressive angiomyxoma was made by meticulous histopathological examination after surgical excision of the mass. This case emphasizes the critical importance of considering aggressive angiomyxoma in the differential diagnosis of vaginal masses, particularly those that do not exhibit invasive characteristics. The case also highlights the need for increased awareness among clinicians about the potential for atypical presentations of this rare tumor, to facilitate timely and accurate diagnosis, and to guide appropriate management strategies. This report contributes to the growing body of literature on aggressive angiomyxoma, highlighting the variability in its presentation and the need to heighten suspicion in atypical cases.

Assessment of PD-1 and PD-L1 tissue expression levels in lichen planus patients: a case-control study.

Programmed cell death protein-1 (PD-1) is an immune checkpoint protein, PD-1 interaction with PD ligand-1 (PD-L1) is essential for maintaining immunological tolerance. The study aimed to study and compare the levels of PD-1 and PD-L1 in lesional and nonlesional skin of lichen planus (LP) patients and compare these levels to normal healthy controls to assess their role in the pathogenesis of LP. This case-control study involved 30 patients with LP and 30 healthy age-and sex-matched controls. After clinical assessment of the severity by LP severity index score (LPSI), skin biopsies were taken from lesional and nonlesional skin of LP patients and from normal skin in healthy controls for assessment of the tissue levels of PD-1 and PD-L1 by ELISA. The tissue levels of both PD-1 and PD-L1 were significantly higher in healthy controls than in both lesional and nonlesional skin of LP patients (P < 0.001). Also, significantly higher PD-l and PD-L1 levels in nonlesional skin than in lesional skin of LP patients were reported (P < 0.001). No significant correlations were found between lesional and nonlesional PD-1, PD-L1 levels, or LPSI score. Based on the fact that PD-1/PD-L1 interaction is important to maintain tolerance and protection against autoimmune diseases, in addition to our study results that revealed lower levels of PD-1/PD-L1 in LP skin than in healthy skin, we can conclude that PD-1/PDL-1 may be incriminated in the pathogenesis of LP. ClinicalTrials.govID: NCT04892381.

Monkeypox infection and pregnancy in lower and middle-income countries: Precautions & recommendations.

Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention.

Evaluation of miRNA-146a, miRNA-34a, and pro-inflammatory cytokines as a potential early indicators for type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

Fractional CO(2) laser treatment vs autologous fat transfer in the treatment of acne scars: a comparative study.

BACKGROUND: Acne scars present a highly challenging and frustrating clinical problem. Fractional CO2 laser treatment has led to marked improvement in scars, and fat transfer, or fat grafting, has also recently proven very useful in regenerative medicine. OBJECTIVE: To compare fractional CO2 laser treatment and fat grafting in the treatment of acne scars. MATERIALS AND METHODS: Twenty patients were included in this study, 10 received 3 sessions of fractional CO2 laser therapy, and 10 received fat grafting. All patients were then followed up for 3 months, and results were assessed with digital photographs taken by a committee of 3 physicians, by a single-blinded physician, and by reports of patient satisfaction. RESULTS: In the fractional CO2 laser treatment group, under 20% of patients were graded as having excellent scar improvement, 0 as having marked scar improvement, under 10% as having mild scar improvement, and almost 70% as having moderate scar improvement. In the fat-grafting group, the scar and overall improvement were graded as 30% excellent, 30% marked, 20% moderate, and 20% mild. CONCLUSION: Fat grafting proved to be more effective in the treatment of acne scars than ablative fractional CO2 laser treatment. There were many points in its favor, the most significant being the clinical improvement in scars and texture. This supports the stem cell theory of adipose tissue in regenerative medicine.