Effect of betulin oil on hair growth in hypothyroidism- a long-term blinded pilot study.

BACKGROUND: One common problem in various patient groups is excessive hair loss on the head. One such group is people struggling with hypothyroidism. The market for preparations for hair growth and hair loss prevention includes betulin. PURPOSE: This pilot study investigated its effect on hair loss in hypothyroid patients. STUDY DESIGN: The study included a group of hypothyroid patients and a control group of people without hypothyroidism. Participants were randomly divided into a group taking placebo and betulin. METHODS: Results were investigated using photographic assessment of hair, trichoscopy and subjective evaluation of participants. CONCLUSION: The study did not conclusively prove that betulin would contribute to the inhibition of hair loss or regrowth.

Level of knowledge, nutritional habits, use of stimulants, and physical activity during the COVID-19 epidemic among students of physiotherapy at Wroclaw Medical University.

OBJECTIVES: The COVID-19 pandemic had a huge effect around the world. The aim of this study was to determine what eating habits, physical activity, and use of stimulants were likely among physical therapy students during the outbreak. METHODS: The 16-65-ComPAN questionnaire for views and eating habits was used. The Fagerström Test was used to determine nicotine dependence, the International Physical Activity Questionnaire to gauge physical activity, and the Alcohol Use Disorders Identification Test to determine alcohol consumption. RESULTS: The results indicated a relatively high percentage of alcohol consumption among this group, as well as a relationship between an unhealthy diet and years of study and smoking. A high value of unhealthy diet and the relationship between dietary knowledge, body mass index, and healthy diet index were also found. No correlation was obtained between the effect of COVID-19 on the student's life and nutritional knowledge and habits, but the percentage of students negatively affected by COVID was high (51%). CONCLUSION: The findings presented here indicate the need to take measures to increase nutritional knowledge among physiotherapy students and to take measures to reduce the use of stimulants.

Physical Activity, Alcohol, and Cigarette Use in Urological Cancer Patients over Time since Diagnosis.

Urological cancers represent a substantial global public health concern, exerting far-reaching effects on both individuals and their families. There is an urgent need to comprehensively understand the transformations in patients' lifestyles and behaviors, given their critical role in the treatment process and overall well-being. This study, involving 128 urological cancer patients, aims to investigate changes in physical activity levels, problematic drinking behaviors assessed through the Alcohol Use Disorders Identification Test (AUDIT), and smoking habits assessed using the Fagerström Test for Nicotine Dependence (FTND) over four distinct time intervals over the subsequent three years from the time of diagnosis and among individuals diagnosed more than three years ago. The results reveal a significant decrease in physical activity levels between study intervals (p < 0.0001), declining from 69% to 45% between the first and second post-diagnosis assessments. Furthermore, the highest levels of problematic substance use, indicated by mean scores, were noted in the first year following diagnosis (AUDIT: 4.20, p = 0.01; FTND: 4.83, p = 0.08). Given the significant impact of physical activity on the prospects of recovery, it is imperative to delve more deeply into the factors contributing to this decline and devise targeted interventions for its improvement. In the context of substance use, it is essential to ascertain whether the initially high levels are a result of coping with the cancer diagnosis or represent a turning point at which patients modify their behaviors and cease their addiction. A more thorough understanding of this phenomenon would enhance the effectiveness of precisely focused interventions.

The Association between the Respiratory System and Upper Limb Strength in Males with Duchenne Muscular Dystrophy: A New Field for Intervention?

Progressive, irreversible muscle weakness is the leading symptom of Duchenne muscular dystrophy (DMD), often resulting in death from respiratory muscle failure. Little is known about the relationship between the functioning of the respiratory system and the hand grip-a function which remains long preserved. This study aimed to investigate the interdependence between muscle strength and the function of both hand grip and the respiratory system in patients with DMD. MATERIALS AND METHOD: The study included cohort patients, aged 6-17, with DMD, recruited from the Rare Disease Centre, Gdansk, Poland. Clinical status (Vignos scale, Brook scale), pulmonary function (respiratory muscle strength-MIP, MEP); spirometry (FEV1; FVC), as well as upper limb function (performance of the upper limb-PUL 2.0) and hand grip strength (HGS) (hand-held dynamometer) were evaluated in all participants. RESULTS: Finally, 53 boys (mean age 11.41 ± 3.70 years, 25 non-ambulant) were included. Each of the participants presented a lower %pv of MIP (48.11 ± 27), MEP (38.11 ± 22), PUL (75.64 ± 27), and HGS (33.28 ± 18). There were differences between the ambulatory and non-ambulatory groups in values of MIP, MEP, FVC, PUL, HGS (p < 0.001 for all), and FEV1 (p < 0.013). There were correlations between PUL, HGS, and MIP (R = 0.56; R = 0.61, p < 0.001 both), MEP (R = 0.59; R = 0.62, p < 0.001), FVC (R = 0.77; R = 0.77, p < 0.001), and FEV1 (R = 0.77; R = 0.79; p < 0.001). These correlations were found for all participants, but non-ambulatory patients presented stronger relationships. CONCLUSIONS: 1. The pulmonary and upper limb functions were within the normal range in ambulatory and low in non-ambulatory patients with DMD, but the muscle strength of both systems was low, regardless of the stage of the disease. 2. There seems to be an interdependence between the respiratory system and upper limb strength in terms of muscle strength and function in DMD patients, which is stronger in non-ambulatory patients. This may be the basis for the creation of a new personalized plan in rehabilitation-the simultaneous rehabilitation of the respiratory and upper limb muscles. Further studies on this theory should be conducted.

Desensitization of transient receptor potential vanilloid type-1 (TRPV1) channel as promising therapy of irritable bowel syndrome: characterization of the action of palvanil in the mouse gastrointestinal tract.

TRPV1 are involved in the control of the gastrointestinal (GI) functions and pain sensation. Their activation induces pain but it is followed by desensitization, which in turn causes analgesia. The studies from the last two decades indicate that TRPV1 are involved in visceral hypersensitivity in the GI tract and pathogenesis of irritable bowel syndrome (IBS). Therefore, the aim of this study is to assess the action of fast desensitizing agonist of TRPV1, palvanil (N-palmitoyl-vanillamine), in the murine GI tract and on nociception to evaluate its potential application in the therapy of IBS. The effect of palvanil on smooth muscle contractility was evaluated using organ baths. The impact of palvanil on intestinal secretion was assessed in Ussing chambers. In vivo, the action of palvanil (0.1-1 mg/kg) was assessed in whole GI transit, fecal pellet output, and colonic bead expulsion tests. The antinociceptive potency of palvanil was tested in the mustard oil-induced pain test. Palvanil inhibited colonic contractions (evoked by electrical field stimulation, EFS) and decreased the ion transport in the colon stimulated with forskolin. It did not affect secretion in experiments with veratridine. In vivo, palvanil prolonged whole GI transit at all doses tested. At the lower dose tested, it accelerated colonic motility during first 60 min following injection. By contrast, at the dose of 1 mg/kg, colonic motility was inhibited. Palvanil induced antinociceptive action at all tested doses in mustard oil-induced pain test. TRPV1 fast-desensitizing compounds, i.e., palvanil, may be promising agents in the therapy of IBS since it modulates intestinal motility and reduces visceral pain.

SPEX airborne spectropolarimeter calibration and performance.

To improve our understanding of the complex role of aerosols in the climate system and on air quality, measurements are needed of optical and microphysical aerosol. From many studies, it has become evident that a satellite-based multiangle, multiwavelength polarimeter will be essential to provide such measurements. Here, high accuracy (∼0.003) on the degree of linear polarization (DoLP) measurements is important to retrieve aerosol properties with an accuracy needed to advance our understanding of the aerosol effect on climate. SPEX airborne, a multiangle hyperspectral polarimeter, has been developed for observing and characterizing aerosols from NASA's high-altitude research aircraft ER-2. It delivers measurements of radiance and DoLP at visual wavelengths with a spectral resolution of 3 and 7-30 nm, respectively, for radiance and polarization, at nine fixed equidistant viewing angles from -56° to +56° oriented along the ground track, and a swath of 7° oriented across-track. SPEX airborne uses spectral polarization modulation to determine the state of linear polarization of scattered sunlight. This technique has been developed in the Netherlands and has been demonstrated with ground-based instruments. SPEX airborne serves as a demonstrator for a family of space-based SPEX instruments that have the ability to measure and characterize atmospheric aerosol by multiangle hyperspectral polarimetric imaging remotely from a satellite platform. SPEX airborne was calibrated radiometrically and polarimetrically using Jet Propulsion Laboratory (JPL) facilities including the Polarization Stage Generator-2 (PSG-2), which is designed for polarimetric calibration and validation of the Airborne Multiangle SpectroPolarimetric Imager (AirMSPI). Using the PSG-2, the accuracy of the SPEX airborne DoLP measurements in the laboratory setup is found to be 0.002-0.004. Radiometric calibration is realized with an estimated accuracy of 4%. In 2017, SPEX airborne took part in the "Aerosol Characterization from Polarimeters and Lidar" campaign on the ER-2 that included four polarimeters and two lidars. Polarization measurements of SPEX airborne and the coflying Research Scanning Polarimeter (RSP), recorded during the campaign, were compared and display root-mean-square (RMS) differences ranging from 0.004 (at 555 nm) up to 0.02 (at 410 nm). For radiance measurements, excellent agreement between SPEX airborne and RSP is obtained with an RMS difference of ∼4%. The lab- and flight-performance values for polarization are similar to those recently published for AirMSPI, where also an intercomparison with RSP was made using data from field campaigns in 2013. The intercomparison of radiometric and polarimetric data both display negligible bias. The in-flight comparison results provide verification of SPEX airborne's capability to deliver high-quality data.

High activity of endogenous opioid system protects against gastric damage development in mouse models of gastric mucosal injury.

BACKGROUND: Gastric mucosal injury appears when acid and pepsin production, simultaneously with inadequate mucosal response, overwhelms protective mechanism in stomach. Here we aimed to explore the linkage between gastric lesion formation and endogenous opioid system activity. METHODS: Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low endogenous opioid system activity were used. Gastric mucosal injury was induced by ethanol (EtOH) and chronic mild stress. To investigate the anti-inflammatory effect of the endogenous opioid system macroscopic score, myeloperoxidase (MPO) activity, the expression of inflammatory molecules as well as oxidative stress markers were determined. Moreover, expression of opioid receptors µ (MOR), κ (KOR) and δ (DOR) at mRNA levels were determined in gastric tissue. RESULTS: High activity of the endogenous opioid system alleviated gastric lesions development in the EtOH-and chronic mild stress-induced mouse gastric mucosal injury models, as demonstrated by decreased macroscopic score in HA line compared to LA. Additionally, antioxidative stress defence mechanisms were positively modulated in both models of gastric mucosal injury. MOR and partially KOR receptors may be responsible for the gastroprotective effect. CONCLUSION: To our knowledge this is the first study to show that increased activity of the endogenous opioid system prevents from gastric lesion formation by influencing - among others - the anti-inflammatory and anti-oxidant mechanisms in the mice stomach. Hence, we suggest that opioids may play an important role in gastric mucosal injury prevention.

Calibration and validation of Airborne Multiangle SpectroPolarimetric Imager (AirMSPI) polarization measurements.

The Airborne Multiangle SpectroPolarimetric Imager (AirMSPI), a precursor to the future Multi-Angle Imager for Aerosols satellite instrument, is a remote-sensing instrument for the characterization of atmospheric aerosols and clouds. To help discriminate between different aerosol particle types, which is crucial to improve our understanding of their impact on climate and air quality, AirMSPI acquires imagery over multiple view angles in the ultraviolet, visible, and near-infrared, and it employs dual photoelastic modulators (PEMs) to target an uncertainty requirement of ±0.005 in the degree of linear polarization (DoLP) at selected wavelengths. Laboratory polarimetric calibrations using a second-generation Polarization State Generator-2 (PSG-2) and validation measurements at 0

Synthesis and activity of opioid peptidomimetics with ß2- and ß3-amino acids.

Morphiceptin (Tyr-Pro-Phe-Pro-NH2) is a selective ligand of the mu opioid receptor, an important target in pain regulation. In this study, morphiceptin was modified at positions 2 or 3 by introduction of ß2- or ß3-amino acids and additionally in position 1 by replacing Tyr by Dmt (2',6'-dimethyltyrosine), which resulted in obtaining enzymatically stable analogs with mixed opioid receptor affinity profiles. An analog of the sequence Dmt-d-Ala-(R)-ß2-1-Nal-Pro-NH2 [Nal=3-(1-naphthyl)-alanine] showed very high activity at the mu and delta receptors in the calcium mobilization functional test but did not cross the artificial membrane imitating the blood-brain barrier. In the in vivo test this analog induced strong antinociceptive effect in the writhing test in mice after intraperitioneal but also oral administration and inhibited diarrhea similarly to loperamide. Therefore, it may become an interesting lead compound in the development of peripherally restricted drugs for the treatment of gastrointestinal disorders.

Fatty acid amide hydrolase (FAAH) inhibitor PF-3845 reduces viability, migration and invasiveness of human colon adenocarcinoma Colo-205 cell line: an in vitro study.

Earlier reports suggest that the endocannabinoids may play a role of endogenous tumor growth modulators. In this study, we investigated whether inhibition of the enzymes involved in the synthesis and degradation of endocannabinoids may reduce colorectal cancer cell invasion and migration. The human colon adenocarcinoma Colo-205 cells were incubated with PF-3845, JZL-184 and RHC-80267 (fatty acid amide hydrolase (FAAH), mono- (MAGL) and diacylglycerol lipase (DAGL) inhibitors, respectively) for 48 h. The MTT colorimetric assay was performed to quantify cell viability. Next, Colo-205 cells were incubated with PF-3845 alone or with PF-3845 together with selected antagonists: AM 251, AM 630, SB 366791, RN 1734 and G-15 (CB1, CB2, TRPV1, TRPV4 and GPR30 antagonists, respectively). Western blot assay was applied to identify the changes in CB1 and CB2 receptor expression. Migration and invasion assays were employed to characterize the effect of PF-3845 on colorectal cancer cell invasion. We found that of all the inhibitors used, the FAAH inhibitor PF-3845 reduced the Colo-205 cell line viability the most effectively (IC50=52.55 µM). We also showed that the effect of decreased cell viability was enhanced when Colo-205 cells were incubated with PF-3845 and RN-1734, a TRPV4 antagonist (IC50=30.54 µM). Western blot assay revealed significantly decreased CB1 receptor expression levels, while CB2 expression was increased in response to PF-3845 when compared to control. Furthermore, PF-3845 inhibited migration and invasion of Colo-205 cell line. These results suggest that pharmacological inhibition of FAAH and consequent enhancement of the endocannabinoid levels may reduce the colorectal cancer growth and progression.

Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome.

OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project. CVS subjects filled out study-specific questionnaires. Single-nucleotide polymorphisms (SNPs) in genes encoding cannabinoid receptors (CNR1 and CNR2), fatty acid amide hydrolase (FAAH) and mu-opioid receptor (OPRM1) were analyzed using the TaqMan SNP genotyping assay. Correlations between SNP's and clinical characteristics of CVS were ascertained. RESULTS: Our study disclosed an increased risk of CVS among individuals with AG and GG genotypes of CNR1 rs806380 (P<0.01), whereas the CC genotype of CNR1 rs806368 and AG and GG genotypes of OPRM1 rs1799971 were associated with a decreased risk of CVS (P<0.05). In addition, AG and GG genotypes of OPRM1 rs1799971 were correlated with migraine episodes, AG and GG of OPRM1 rs1799971, and CT and CC of CNR1 rs806368 with a family history of migraines (second degree relatives), and CT and CC of CNR1 rs2023239 with a positive response to therapy. CONCLUSIONS: Our results show for the first time that the variations in CNR1 and OPRM1 genes are associated with CVS and that different genotypes may contribute to the risk of CVS.

Methyl-orvinol-Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. METHODS: In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. RESULTS: Methyl-orvinol (10-10 to 10-6M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and ß-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. CONCLUSION: Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D.

Polymorphisms of homologous recombination RAD51, RAD51B, XRCC2, and XRCC3 genes and the risk of prostate cancer.

Genetic polymorphisms in DNA repair genes may induce individual variations in DNA repair capacity, which may in turn contribute to the risk of cancer developing. Homologous recombination repair (HRR) plays a critical role in maintaining chromosomal integrity and protecting against carcinogenic factors. The aim of the present study was to evaluate the relationship between prostate cancer risk and the presence of single nucleotide polymorphisms (SNPs) in the genes involved in HRR, that is, RAD51 (rs1801320 and rs1801321), RAD51B (rs10483813 and rs3784099), XRCC2 (rs3218536), and XRCC3 (rs861539). Polymorphisms were analyzed by PCR-RFLP and Real-Time PCR in 101 patients with prostate adenocarcinoma and 216 age- and sex-matched controls. A significant relationship was detected between the RAD51 gene rs1801320 polymorphism and increased prostate cancer risk. Our results indicate that the RAD51 gene rs1801320 polymorphism may contribute to prostate cancer susceptibility in Poland.

Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome.

INTRODUCTION: Constipation-predominant irritable bowel syndrome (IBS-C) is a common functional gastrointestinal (GI) disorder characterized by recurrent abdominal pain and prolonged GI transit. The pathogenesis of IBS-C has still not been established; therefore, drugs currently in use in IBS-C act mainly symptomatically, whereas novel pharmacological targets are urgently needed. Tenapanor is a potent inhibitor of Na(+)/H(+) exchanger 3 [NHE3], localized in the apical membrane of intestinal epithelial cells. NHE3 participates in the uptake of sodium ions and water from the intestinal lumen. AREAS COVERED: In this review, the authors discuss pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies. They also summarize clinical trials on tenapanor's safety and efficacy in view of its potential role in IBS-C therapy. EXPERT OPINION: Tenapanor possesses an excellent preclinical safety profile and, as of now, there are no serious concerns about its side effects. The non-systemic action of tenapanor constitutes a significant advantage, as it minimizes possible adverse effects or drug-drug interactions. However, Phase III clinical trials are still needed to confirm results obtained in earlier phases and optimize the dose-response for tenapanor, whereas limiting diarrhea, its major adverse effect.

Beneficial Effects of Probiotics, Prebiotics, Synbiotics, and Psychobiotics in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a group of diseases characterized by inflammation of the small and large intestine and primarily includes ulcerative colitis and Crohn's disease. Although the etiology of IBD is not fully understood, it is believed to result from the interaction of genetic, immunological, and environmental factors, including gut microbiota. Recent studies have shown a correlation between changes in the composition of the intestinal microbiota and IBD. Moreover, it has been suggested that probiotics and prebiotics influence the balance of beneficial and detrimental bacterial species, and thereby determine homeostasis versus inflammatory conditions. In this review, we focus on recent advances in the understanding of the role of prebiotics, probiotics, and synbiotics in functions of the gastrointestinal tract and the induction and maintenance of IBD remission. We also discuss the role of psychobiotics, which constitute a novel class of psychotropic agents that affect the central nervous system by influencing gut microbiota.

Role of G protein-coupled orphan receptors in intestinal inflammation: novel targets in inflammatory bowel diseases.

A large number of proteins were classified into the family of G protein-coupled receptors (GPCRs). Based on their characteristic serpentine domain, they are called 7 TM receptors. Presently, their ligands and physiological functions remain unknown. In this review, we summarize what is known on these receptors and discuss the potential use of these orphan GPCRs (GPRs) in the induction or maintenance of remission in inflammatory bowel diseases. We focus on GPRs 30, 41, 43, 55, 119, and 120, where scientific evidence supports a potential role in intestinal inflammation.

Role of transient receptor potential channels in intestinal inflammation and visceral pain: novel targets in inflammatory bowel diseases.

Transient receptor potential (TRP) channels are a large group of ion channels that are prevalent in mammalian tissues. They are widely distributed in the central and peripheral nervous systems, and in nonneuronal cells, where they are implicated in sensing temperature, noxious substances, and pain. TRPs play an important role in immune response and nociception and, therefore, may be involved in the pathogenesis of inflammatory bowel diseases, whose major symptoms include chronic inflammatory state and abdominal pain. In this review, we summarize what is known on TRP channels in inflammatory bowel disease and visceral pain; we focus in particular on TRPV1, TRPV4, TRPA1, and TRPM. We also analyze scientific reports that evidence potential use of TRP regulators in future inflammatory bowel disease treatment.

Locked nailing for metastatic disease of the long bones.

Material and methods. Between 1996 and 2002, a total of 21 patients were treated with intamedullary nailing for metastatic tumors (12 men and 9 women) without view of pathological fractures. Average patients age at operation was 68,9 (range 21-80). The primary origin of metastatic tumors was: renal cancer most common 6 times, breast cancer 5, lung cancer 4, prostate cancer 2, cervical cancer 1. We included 3 patients with lymphoma to clinical materials. The humerus was involved in 13 cases, femur 7, tibia 1 of metastatic tumors.
Results. The time of patients life from the operation time depended on the type of neoplasm: breast - 5 months, kidney - 5 months, lung - 3 months, prostate - 16,5 months, myeloma - 16 months, uterus - 6 months. The mean was 7,5 months.
Conclusions. The average postoperative survival period was 7,5 months. There were no embolism or thrombosis complications. All patients were given professional oncological advice and were treated palliatively.