Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits.

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

Numerical and experimental evaluation of nasopharyngeal aerosol administration methods in children with adenoid hypertrophy.

Administering aerosol drugs through the nasal pathway is a common early treatment for children with adenoid hypertrophy (AH). To enhance therapeutic efficacy, a deeper understanding of nasal drug delivery in the nasopharynx is essential. This study uses an integrated experimental, numerical modelling approach to investigate the delivery process of both the aerosol mask delivery system (MDS) and the bi-directional delivery system (BDS) in the pediatric nasal airway with AH. The combined effect of respiratory flow rates and particle size on delivery efficiency was systematically analyzed. The results showed that the nasopharyngeal peak deposition efficiency (DE) for BDS was approximately 2.25-3.73 times higher than that for MDS under low-flow, resting and high-flow respiratory conditions. Overall nasopharyngeal DEs for MDS were at a low level of below 16 %. For each respiratory flow rate, the BDS tended to achieve higher peak DEs (36.36 % vs 9.74 %, 37.80 % vs 14.01 %, 34.58 % vs 15.35 %) at smaller particle sizes (15 µm vs 17 µm, 10 µm vs 14 µm, 6 µm vs 9 µm). An optimal particle size exists for each respiratory flow rate, maximizing the drug delivery efficiency to the nasopharynx. The BDS is more effective in delivering drug aerosols to the nasal cavity and nasopharynx, which is crucial for early intervention in children with AH.

Maximal medical treatment of adenoid hypertrophy: a prospective study of preschool children.

PURPOSE: This study aimed to examine the effectiveness of the combined maximal medical treatment for adenoid hypertrophy in preschool children. METHODS: Sixty-four children underwent one-year combined therapy with intranasal mometasone furoate, oral desloratadine, nasal saline irrigation, and bacteriotherapy. Additionally, decongestion drops were applied during scheduled breaks. RESULTS: Of the 64 treated children, 72% showed clinical improvement in adenoid symptoms while 28% did not improve and underwent surgery. These groups differed significantly in terms of the overall reduction in ailments after treatment (p < 0.001), infection rate (p < 0.001), catarrh severity (p < 0.001) and nasal patency (p < 0.001). Endoscopic examination confirmed that responders experienced, on average, a decrease of 8.4% in the adenoid/choana ratio and an improvement in mucosal coverage of the adenoid. These effects were not observed in the group of children whose parents opted for surgery after nine months of conservative treatment. CONCLUSIONS: The proposed new schema of long-term maximal medical treatment with the use of combined intermittent treatment of intranasal mometasone furoate and decongestion drops, oral desloratadine, nasal saline irrigation, and bacteriotherapy can be attempted in patients with adenoid hypertrophy symptoms, and responders may avoid the need for surgery. The applied treatment breaks resulted in a low number of therapeutic side effects.

Simvastatin Significantly Reduced Alcohol-Induced Cardiac Damage in Adolescent Mice.

Alcohol abuse by adolescents is becoming a serious health concern as they often progress to becoming alcoholics later in life which may lead to heart problems. Chronic alcohol use alters the cardiac function and structure, such as haemodynamic changes, weakening and loss of cardiomyocytes, myocardial fibrosis, and inflammation. Simvastatin is a commonly used drug for the treatment and management of various cardiovascular problems but information on its protective effects against alcohol-induced cardiomyocyte hypertrophy, fibrosis, and inflammation is lacking in the literature. Four-week-old male (n = 5) and female (n = 5) C57BL/6 J mice were assigned to each experimental group: (I) NT-no administration of alcohol or Simvastatin; (II) ALC-2.5 g/Kg/day of 20% alcohol via intraperitoneal injection (i.p.); (III) SIM-5 mg/Kg/day of Simvastatin via oral gavage; (iv) ALC + SIM5-5 mg/Kg/day of Simvastatin via oral gavage followed by 2.5 g/Kg/day of 20% alcohol via i.p.; and (v) ALC + SIM15-15 mg/Kg/day Simvastatin via oral gavage followed by 2.5 g/Kg/day of 20% alcohol via i.p. After the 28-day treatment period, the heart was removed and processed for H&E, Masson's trichrome, or TNF-α immunolabelling. The area and diameter of cardiomyocytes were measured on the H&E-stained sections. The distribution of collagen or TNF-α expression was quantified using the deconvolution tool of ImageJ software. The results confirmed alcohol-induced toxicity on the cardiomyocytes and Simvastatin reduced alcohol-induced cardiomyocyte hypertrophy, fibrosis, and inflammation in both sexes. This study demonstrated that Simvastatin, an FDA approved and easily accessible drug, may be beneficial in lowering the prevalence of alcohol-induced cardiovascular diseases (especially in adolescents) which will have a huge financial implication on health systems worldwide.

Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation.

OBJECTIVES: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls. METHODOLOGY: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Sídák's multiple comparisons test was used to compare groups. RESULTS: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment. CONCLUSION: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

Individualized Homeopathic Medicines in the Management of Symptomatic Adenotonsillar Hypertrophy in Children: A Prospective Observational Study.

BACKGROUND: Globally, adenotonsillar hypertrophy (ATH) is one of the most prevalent upper respiratory tract disorders of children, with associated troublesome symptoms such as sleep apnea and cognitive disturbances. In this study, we evaluated the potential role of individualized homeopathic medicines in the management of symptomatic ATH in children. METHODS: A multicenter prospective observational study was conducted at five institutes under the Central Council for Research in Homoeopathy, India. Primary and secondary outcomes (symptom score for adenoids, other symptoms of ATH, Mallampati score, tonsillar size, Sleep-Related Breathing Disorder of the Paediatric Sleep Questionnaire [SRBD-PSQ]) were assessed through standardized questionnaires at baseline and at 3, 6, 9 and 12 months. Radiological investigations for assessing the adenoid/nasopharyngeal (A/N) ratio were carried out at baseline, 6 and 12 months. All analyses were carried out using an intention-to-treat approach. RESULTS: A total of 340 children were screened and 202 children suffering from ATH were enrolled and followed up monthly for 12 months. Each patient received individualized homeopathic treatment based on the totality of symptoms. Statistically significant reductions in adenoid symptom score, Mallampati score (including tonsillar size), SRBD-PSQ sleep quality assessment and A/N ratio were found over time up to 12 months (p < 0.001). Homeopathic medicines frequently indicated were Calcarea carbonicum, Phosphorus, Silicea, Sulphur, Calcarea phosphoricum, Pulsatilla, Lycopodium and Tuberculinum. No serious adverse events were recorded during the study period. CONCLUSION: This study suggests that homeopathic medicines may play a beneficial role in the management of symptomatic ATH in children. Well-designed comparative trials are warranted.

The Volumetric Effect of Botulinum Toxin Type A Injection on the Parotid Gland: A Randomized Controlled Trial.

BACKGROUND: Botulinum neurotoxin type A (BTX-A) to the masseter muscle is a useful tool for the aesthetic narrowing of the width of the lower face. The administration of BTX-A to visible parotid glands is also effective to reduce lower facial width. However, no studies have quantitatively analyzed the effect of BTX-A on the parotid glands. METHODS: The purpose of this study was to confirm the impact of BTX-A injection on the parotid gland and to suggest the effective dosage of BTX-A in facial slimming. This study was conducted by selecting patients who desired facial slimming from among patients who required surgery for a facial bone fracture. Patients undergoing BTX-A injection were randomized to high-dose, low-dose, and placebo groups, and different doses of BTX-A for each group were injected into both parotid glands during facial bone surgery. RESULTS: A total of 30 patients were enrolled in this study. Ten patients in the high-dose group, eight in the low-dose group, and nine in the control group completed the clinical trial. There were significant changes in both the high- and low-dose groups compared with the control group ( P < 0.001, P < 0.001), and in interaction of time and group ( P < 0.001). Volume recovery after 3 months was found in 7.6% in the high-dose group and in 4.8% in the low-dose group. CONCLUSION: BTX-A injection into parotid glands can be an effective treatment option in managing salivary gland enlargement for lower face contouring. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Do repetitive botulinum neurotoxin injections induce muscle fibrosis? Sonographic observation of the masseter muscle.

OBJECTIVE: In the esthetic field, the masseter muscle is commonly targeted by botulinum neurotoxin for facial contouring. However, multiple botulinum neurotoxin injections have been reported to cause muscle fibrosis. Ultrasonography can be useful for clinical consideration in such cases. MATERIALS AND METHODS: This study presents nine cases of masseteric fibrosis caused by repeated botulinum neurotoxin injections with ultrasonographic analysis of full and partial masseteric fibrosis. RESULTS: Repetitive botulinum neurotoxin injections resulted in reduced masseter muscle volume, which frequently appeared hyperechoic on ultrasonography. The hyperechoic region was mostly located in the deep and posterior portions; however, in some cases, it was observed throughout the muscle, including the superficial, deep, or both areas. CONCLUSION: The fibrotic masseter muscles appear hyperechoic, and ultrasonography is necessary to analyze the degree and location of fibrosis. Predictions can be made for cases in which botulinum neurotoxin injections may have less of an effect after ultrasonography. Because muscle fibrosis can be localized, it is necessary to confirm the degree and location of fibrosis before determining the effective area of injection. In clinical practice, muscle fibrosis may be visible in a specific area where blind injections are administered.

Topical administration of S. salivarius 24SMB-S. oralis 89a in children with adenoidal disease: a double-blind controlled trial.

Chronic adenoiditis (CA) is generally sustained by some infectious foci mainly located within the nasopharynx or in the deep adenoidal pads and it is characterized by a complex interplay between bacterial species. The aim of this study was to assess the efficacy and safety of the topical nasal administration of a probiotic compound based on S. salivarius 24SMB and S. oralis 89a in children with CA in terms of reduction in: the number of acute adenoidal infections (primary outcome), and in the blockage of the nasopharynx space by hypertrophic adenoids (secondary outcome). A prospective, double-blind, 1:1 randomized controlled study was performed to test the effectiveness of a 90-day treatment with Rinogermina spray (DMD ITALIA s.r.l, Rome), 1 puff each nostril twice a day for 90 days, to nasal spray placebo in children with CA (in terms of number of acute exacerbations and blockage of nasopharynx space assessed after 90 days of treatment- T1, and 90 days later- T2). The final analysis was based on 152 children (males = 48.0%; mean age = 49.2 ± 14.1 months). Compared to the baseline, no significant differences in terms of number of acute exacerbations at T1 and T2 follow-up visits were detected in both groups. After treatment, a significant reduction in the blockage of nasopharynx space by hypertrophic adenoids (0.002 < p-value < 0.007) compared to the baseline was attested in the study group at T1 and T2, but not in the control group. CONCLUSIONS: Our findings document a positive effect of Rinogermina spray in achieving reduction in the blockage of nasopharynx space by hypertrophic adenoids, thus suggesting that its use into the integrated therapeutic management of children with CA could be of a certain utility. WHAT IS KNOWN: • Chronic adenoiditis in children results from an imablance in baterial homeostasis at the nasophaynx, with impairment in respiratory microbiota. • The modulatory effect of target transnasal bacteriotheray by means of S. salivarius has been considered in children with chronic adenoiditis in children with recurrent acute otitis media with preliminary positive results. WHAT IS NEW: • This randomized controlled study, specifically designed on a cohrt of children with chronic adenoiditis, documents a certain effectiveness of the probiotic treatment in achieving a reduction in the grade of adenoidal hypertropy, compared to placebo.

Classification of gastrocnemius muscle hypertrophy for personalized botulinum toxin type A treatment.

BACKGROUND: Owing to its safety and convenience, botulinum toxin type A (BoNtA) has become a first-choice treatment for contouring calf muscle asymmetries or deformities. Different injection methods and dosages have been discussed in the literature, but a standardized BoNtA treatment remains unclear. AIMS: This study aimed to classify gastrocnemius muscle hypertrophy (GMH) through multiple measurements to provide a personalized BoNtA treatment protocol. METHODS: The measurements combining of gastrocnemius muscle (GM) contour, max leg circumference and GM thickness was applied to classify different type of GMH in a normal population. Based on these findings, a personalized BoNtA treatment protocol was determined and evaluated regarding max leg circumference, GM thickness, the position of max leg circumference, patient and doctor satisfaction rate, and complications. RESULTS: A total of 100 GMH were classified into two bulging types (bilateral-bulging type and unilateral-bulging type) and two categories (moderate GMH and severe GMH). 40 cases were treated with personalized BoNtA injection methods ("Even" or "Intense"method) and dosages (300 or 400 units). Follow-up examinations at 1, 3, and 6 months after treatment. Max leg circumference and GM thickness decreased significantly and the position of max leg circumference rose prominently during treatment (2.56 ± 1.93; p < 0.05). The overall patient satisfaction rate was 70%-100%. No serious complications occurred. CONCLUSIONS: We identify four groups of GMH through several measurements and outline a personalized BoNtA treatment for each type. This recommended protocol may improve the therapeutic outcomes and patient satisfaction after treatment.

Medical treatment does not reduce surgery rates in children with adenoid hypertrophy.

OBJECTIVE: We sought to study adenoidectomy rates in children with adenoid hypertrophy (AH) who were either treated with medical therapy or not during a 2-year follow-up period in a longitudinal population-based study. METHODS: We retrospectively identified healthy children aged 1-18 years between 2014 and 2020 with AH diagnosis from the Clalit Health Services database, the largest healthcare maintenance organization in Israel. The main outcome was adenoidectomy alone or in combination with other procedures performed within 2 years after diagnosis. The treatment group consisted of children who received medical therapy, defined as a pharmacy purchase of montelukast, nasal steroid sprays and/or antihistamines (medical therapy aimed to reduce AH) for ≥2 consecutive months, while the control group consisted of untreated children. RESULTS: We identified 68,356 unique children with AH, of them 56 % were boys, with a mean age of 4.9 ± 3.3 years. Of them, 5310 (7.7 %) received medical therapy. Overall, 6633 (9.7 %) underwent adenoidectomy within 2 years following diagnosis. There was no significant difference in surgery referral rates between the treatment and the control groups, 10 % vs. 9.7 %, respectively (p = 0.3). When adjusted for age and sex, the likelihood of undergoing adenoidectomy was similar in both groups (HR = 0.98, 95 % CI = 0.90-1.07, p = 0.6). Among operated children, the average time from diagnosis to surgery was statistically significantly longer in the treatment group than in the control group, 346 ± 180 vs 311 ± 175 days (p < 0.001). CONCLUSION: Prescribing montelukast, nasal steroids and/or oral antihistamines was not associated with a reduction in adenoidectomy rates and was associated with an average surgery delay of 35 days.

[Treatment with botulinum toxin of masseter hypertrophy, myalgia of the tendons and attrition induced by bruxism]. / Behandeling van bruxismegeïnduceerde masseterhypertrofie, tendomyalgie en attritie met botulinetoxine.

Bruxism is a disabling condition in which unconscious contractions of the masticulatory muscles lead to teeth grinding and jaw clenching. Symptoms include toothache, temporomandibular dysfunction, headache and attrition. Treatment options range from conservative approaches to invasive interventions. Education, stress reduction, avoidance of stimulants, and relaxation techniques can help in mild cases. Wearing an occlusal splint can reduce attrition. Botulinum neurotoxin type A (BoNT-A) injections are a treatment option temporarily causing partial paralysis of the masticulatory muscles. BoNT-A is a treatment for reducing symptoms and improving the quality of life of patients with bruxism that has been proven safe and effective. The effects usually last several months. To achieve the best results and minimize side effects, BoNT-A injections should be applied by an experienced practitioner.

Sacubitril/valsartan attenuates myocardial inflammation, hypertrophy, and fibrosis in rats with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) represents a multifaceted syndrome related to complex pathologic mechanisms. Sacubitril/valsartan (Sac/val) has demonstrated therapeutic efficacy in HFpEF treatment. However, additional research is required to elucidate its pharmacological mechanisms. Accordingly, this study aimed to explore the potential therapeutic effects of Sac/val in HFpEF rats and the underlying molecular mechanisms. In this study, rats with HFpEF were induced by subjecting spontaneously hypertensive rats to a diet rich in fats, salts, and sugars, along with administering streptozotocin. Subsequently, they were administered Sac/val at a daily dosage of 18 mg/kg. Finally, cardiac structure and function were assessed using echocardiography; Hematoxylin and eosin staining and Masson's trichrome staining were employed to evaluate the pathological changes; Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to determine the expression of pertinent mRNA and proteins. Sac/val treatment attenuated left ventricular (LV) remodeling and diastolic dysfunction in HFpEF rats, possibly related to its anti-inflammatory, anti-hypertrophic, and anti-fibrotic efficacy. Mechanistically, Sac/val might inhibit inflammation by down-regulating cell adhesion molecule (intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1)) expression. Additionally, it blocked the phosphorylation of glycogen synthase kinase 3ß (GSK-3ß) to prevent cardiomyocyte hypertrophy. Furthermore, it effectively suppressed myocardial fibrosis by inhibiting the transforming growth factor-beta1 (TGF-ß1)/Smads pathway. Our findings suggest that Sac/val improved LV remodeling and diastolic dysfunction, potentially attributed to its anti-inflammatory, anti-hypertrophic, and anti-fibrotic effects. These results provide a sound theoretical rationale for the clinical application of Sac/val in patients with HFpEF.

Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.

Experts' recommendations in laser use for the endoscopic treatment of prostate hypertrophy: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training-Research in Urological Surgery and Technology (T.R.U.S.T.)-Group.

PURPOSE: To identify expert laser settings for BPH treatment and evaluate the application of preventive measures to reduce complications. METHODS: A survey was conducted after narrative literature research to identify relevant questions regarding laser use for BPH treatment (59 questions). Experts were asked for laser settings during specific clinical scenarios. Settings were compared for the reported laser types, and common settings and preventive measures were identified. RESULTS: Twenty-two experts completed the survey with a mean filling time of 12.9 min. Ho:YAG, Thulium fiber laser (TFL), continuous wave (cw) Tm:YAG, pulsed Tm:YAG and Greenlight™ lasers are used by 73% (16/22), 50% (11/22), 23% (5/22), 13.6% (3/22) and 9.1% (2/22) of experts, respectively. All experts use anatomical enucleation of the prostate (EEP), preferentially in one- or two-lobe technique. Laser settings differ significantly between laser types, with median laser power for apical/main gland EEP of 75/94 W, 60/60 W, 100/100 W, 100/100 W, and 80/80 W for Ho:YAG, TFL, cwTm:YAG, pulsed Tm:YAG and Greenlight™ lasers, respectively (p = 0.02 and p = 0.005). However, power settings within the same laser source are similar. Pulse shapes for main gland EEP significantly differ between lasers with long and pulse shape modified (e.g., Moses, Virtual Basket) modes preferred for Ho:YAG and short pulse modes for TFL (p = 0.031). CONCLUSION: Ho:YAG lasers no longer seem to be the mainstay of EEP. TFL lasers are generally used in pulsed mode though clinical applicability for quasi-continuous settings has recently been demonstrated. One and two-lobe techniques are beneficial regarding operative time and are used by most experts.

The sodium borate relieves the hypertrophic damage induced during pregnancy, it improves contractibility, reduces oxidative stress and stimulates cell proliferation.

INTRODUCTION: Fetal and postnatal hypertrophy develop in response to such different exposures or illnesses the mother suffers during gestation as anti-infectious and physical agents, obesity, hypertension, diabetes, and even advanced maternal age. This gives rise to high comorbidities in the newborn; therefore, looking for alternatives that contribute to cardiac homeostasis is quite necessary to inhibit the overgrowth of myocytes. Boron-derivative compounds could play a key role in exerting a repairing effect on chronic cardiac damage induced during gestation. METHODOLOGY: The cardiotoxic effect of 6.4, 12 and 100 mg/kg of sodium tetraborate administered by oral delivery route to healthy pregnant mice was assessed. After that, the use of the chemical compound was tested in the treatment of pregnant mice previously subjected to isoproterenol (fetal hypertrophy model) on the fifth day post coitus. Prior to the sacrifice of the pups of mice an electrocardiography (ECG) was done. Morphological and histological changes of heart were assessed in newborn pups. As a damage marker, the concentration of p38 nitrogen-activated protein kinases were evaluated by using Western Blot and the levels of malondialdehyde (MDA) as well as glutathione antioxidants (GSH) and glutathione peroxidase (GPx) were tested by spectrometry. Moreover, the mRNA expression for early response genes (c-jun, c-fos y c-myc), late response (GATA-4, Mef2c, NFAT) and heart damage (ANP and BNP) was measured by qPCR real time. RESULTS: The supply of 6,4 and 12 mg/kg-sodium tetraborate favored ventricular remodeling with histological alterations. By comparison, 100 mg/kg of sodium tetraborate administered during the fetal stage did not alter neither the cardiac morphology of six-week old pups nor the p38/P-p38MAPK ratio remained the same and no oxidative stress was observed. When pregnant females treated with isoproterenol were treated with 100 mg/kg sodium tetraborate during the fetal stage, an improvement in contractility was detected in the pups with an actual reduction in myocardial fibrosis and oxidative stress, but cardiac mass increased. In addition, the expression levels of c-jun, c-myc, GATA-4, MEF2c and ANP mRNA declined in comparison with CTR. However, the hypertrophic damage mechanism was sustained by c-fos, NFAT and BNP expressions. CONCLUSIONS: The set of results achieved suggests that high concentrations of sodium tetraborate have no cardiotoxic effects. Furthermore, sodium tetraborate mitigates hypertrophy induced during pregnancy, thereby improving contractibility, reducing oxidative stress and stimulating cell proliferation. Therefore, sodium tetraborate could be an excellent prophylactic treatment administered by delivery oral route during pregnancy when there is a risk of developing fetal left ventricular hypertrophy (LVH).

Immune-related gigantomastia: a case study.

PD-1/PDL-1 inhibitors have revolutionized cancer treatment, especially in lung cancer. Despite their efficacy, a new spectrum of side effects, called immune-related adverse events, may occur and their management could be difficult. Gigantomastia, a rare condition characterized by excessive growth of the breasts, has been associated with some drugs, but no correlation with immunotherapy has ever been reported. Here, we report the case of a possible immune-related gigantomastia.

A person with a type of lung cancer called non-small-cell lung cancer might get treated with a special drug called nivolumab. This drug helps the body's immune system fight the cancer. However, even though these new drugs work well, they can sometimes cause side effects. Some of these side effects are very rare and hard to predict. In one case, a patient who took nivolumab developed a condition called gigantomastia. This means their breasts became unusually large. The doctors checked for other possible causes, but couldn't find any. Gigantomastia is already a very rare condition by itself. What's even more interesting is that nobody has ever reported gigantomastia as a side effect of immunological therapies before. Researchers still don't know why it happened in this case. This episode is worth mentioning because it's a very unusual and unique case.

Clinical investigation of botulinum toxin (prabotulinumtoxin A) for bruxism related to masseter muscle hypertrophy: A prospective study.

This study aims to confirm the effectiveness and safety of a prabotulinumtoxin type A (praBTX-A) injection in patients with bruxism and masseter hypertrophy. The study included patients who ground or clenched their teeth while sleeping and had computed tomography (CT) scans that showed a maximum thickness of the masseter muscle of 15 mm or more. The praBTX-A was administered bilaterally into the masseter muscles; 15 U/side for group 1, 25 U/side for group 2, and 35 U/side for group 3. CT scans and bruxism questionnaires were conducted before and eight weeks after the injection. Thirty-seven patients were enrolled, but three dropped out due to loss of follow-up. After injection, masseter thickness decreased to 15.1 ± 2.0 mm for group 1, 14.3 ± 2.9 mm for group 2, and 13.4 ± 1.8 mm for group 3 (p = 0.043). Group 3 showed a statistically significant lower masseter thickness compared to group 1 (p = 0.039). Both subjective and objective frequencies of bruxism decreased for all groups, but there were no significant differences in either subjective (p = 0.396) or objective frequencies (p = 0.87) between the groups after the injection. The results of this study suggest that praBTX-A injection is a safe and effective treatment for bruxism and masseter hypertrophy. A dosage of 35 IU/side can effectively decrease masseter thickness and relieve bruxism symptoms. Even the minimum dosage of 15 IU/side can contribute to improvements in bruxism symptoms. This investigation provides valuable information for managing bruxism that is associated with hypertrophic masseter muscles.

Selective Neurocoagulation of Gastrocnemius and Lateral Soleus Muscles for Calf Reduction.

BACKGROUND: Various methods have been attempted to improve the size and shape of calves, and selective neurocoagulation of the calf muscle using radio frequency (RF) is one of them. The objective of this study was to provide information about the efficacy and safety of selective neurocoagulation of the gastrocnemius (GCM) and lateral soleus muscles using RF for cosmetic purposes. METHODS: A retrospective analysis of 345 patients (686 legs), who underwent selective neurocoagulation using RF at our clinic for calf hypertrophy between January 2018 and March 2020, was performed. We measured the circumference of the calf and thickness of the medial GCM using ultrasonography before and after the procedure. Patient satisfaction and side effects were investigated through interviews. RESULTS: The average calf circumference had decreased by 2.9 ± 1.1 cm (GCM-only group) and 3.0 ± 1.4 cm (GCM + lateral soleus group), at 6 months after the procedure, and there was a statistically significant decrease in both groups. At 12 months after the procedure, the calf circumference slightly increased compared to that at 6 months, but the circumference was still smaller than that before the procedure. Most patients were satisfied with the size and contour of their calves and there were no severe adverse effects. CONCLUSIONS: Motor nerve coagulation using RF was effective in reducing the volume of the GCM and lateral soleus muscles and softening the contours of the calf. It was safe and without side effects in most patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine.

Hypertension is a modifiable cardiovascular risk factor and cause of death worldwide. Lotusine, an alkaloid extracted from a plant used in traditional Chinese Medicine, has shown anti-hypertensive effects. However, its therapeutic efficacy requires further investigation. We adopted integrated network pharmacology and molecular docking approaches with the aim of investigating lotusine's antihypertensive effects and mechanisms of action in rat models. After identifying the optimal intravenous dosage, we observed the effects of lotusine administration on two-kidney, one-clip (2K1C) rats and spontaneously hypertensive rats (SHRs). Based on network pharmacology and molecular docking analyses, we measured renal sympathetic nerve activity (RSNA) to evaluate lotusine's effect. Finally, an abdominal aortic coarctation (AAC) model was established to evaluate lotusine's long-term effects. The network pharmacology analysis identified 21 intersection targets; of these, 17 were also implicated by the neuroactive live receiver interaction. Further integrated analysis showed high lotusine affinity for the cholinergic receptor nicotinic alpha 2 subunit, adrenoceptor beta 2, and adrenoceptor alpha 1B. Blood pressure of the 2K1C rats and SHRs decreased after treatment with 2.0 and 4.0 mg/kg of lotusine (P < 0.001 versus saline control). We also observed RSNA decreases consistent with the network pharmacology and molecular docking analysis results. Results from the AAC rat model indicated that myocardial hypertrophy was decreased with lotusine administration, demonstrated by echocardiography and hematoxylin and eosin and Masson staining. This study provides insights into the antihypertensive effects and underlying mechanisms of lotusine; lotusine may exert long-term protective effects against myocardial hypertrophy caused by elevated blood pressure.