4th Week Of Treatment Research Articles

Cariprazine in Hospital Treatment of Acute Psychotic Conditions Due to Comorbid Schizophrenia and Chemical Addictions

Background: endogenous psychoses complicated with different addictions have special psychopathological structure including delirious episodes, true hallucinations combined with typical positive symptoms of schizophrenia. These cases are difficult for treatment due to non-compliance of patients and their bad tolerance to drugs. The aim was to study the most effective psychopharmacological treatment using cariprazine for acute psychotic states in paranoid schizophrenia combined with chemical addictions. Patients and Methods: the study was conducted at psychiatric hospitals of Tomsk region, St. Petersburg, Nizhnevartovsk and Noyabrsk from 2018 to 2024. 208 men aged 18 to 45 years suffering from paranoid schizophrenia and dependent on psychoactive substances were examined. The main group made up 104 in-patients, who took cariprazine alone or in combination with haloperidol or chlorpromazine. The control group included 104 in-patients treated with other antipsychotics (aripiprazole, risperidone, olanzapine). Research methods: clinical and psychopathological, psychometric (PANSS, SANS, CGI, GAF), statistical (Python 3.11.0; R version 3.2.4; SPSS Statistics Base 22.0). Results: It was revealed that when comparing the control group with the main group, similar indicators were observed on the CGI and GAF scales on the 2nd week of the study, and on the 4th week of the study, compared with the control group, an improvement in indicators on the PANSS, SANS, CGI, GAF scales was observed. Conclusions: Cariprazine, compared with other atypical antipsychotics (risperidone, olanzapine, aripiprazole), showed a distinct antipsychotic effect in the treatment of acute psychotic states in patients with schizophrenia dependent on psychoactive substances. By the end of the 2nd week after hospitalization, when treating with cariprazine at an average dose of 3 to 6 mg/day in combination with typical neuroleptics (haloperidol, chlorpromazine) or a tranquilizer, the most pronounced antipsychotic effect is achieved. Subsequent isolated use of cariprazine at a therapeutic dose of 3–4.5 mg/day has an effect similar to that of leading atypical antipsychotics by the end of the 4th week of treatment. Unlike other atypical antipsychotics, cariprazine was more effective in the treatment of negative symptoms of schizophrenia, which made it possible to achieve an improvement in overall functioning, increase the duration of remission, and reduce the risk of rehospitalization and the development of hospitalism.

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice.

The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

Alverin with Simethicone Combination: Efficacy and Safety Clarification in Overlap Syndrome (Dyspepsia with Nonspecific/ Unspecified Irritable Bowel Syndrome) by Patients’ Self-assessment

The study results showed the high efficiency of the combination in one form of two active substances- alverine (alverine) and simeticone (simeticone)-in the drug Meteospasmyl according to the results of self-assessment by patients with overlapping symptoms of uninvestigated dyspepsia(UD) and nonspecific irritable bowel syndrome(IBS-N), with a positive effect of 86.7% (95% CI Fisher’s 78.6–92.5) cases and a high Odds ratio (chance) (22.7, at 95% CI 8.9–58.4) of the effect compared with the comparator group (treatment without the use of Meteospasmyl). Treatment adherence higher in 12 times (Odds ratio) (95% CI 1.42– 112.06) with Meteospasmyl (85.7% (95% CI 63.7–97.0)), versus the comparator group (33.3% (95% CI 7.5–70.1)). Thus, Meteospasmyl can be used as a first-line drug in overlapping dyspepsia with an nonspecific variant of irritable bowel syndrome, especially during the period of performing and waiting for the results of the patient’s clarifying examination. A high safety degree of this drug has been demonstrated, both in terms of clinical and laboratory parameters. Results were obtained confirming the effect of Meteospasmyl on skeletal muscles with a significant increase in the grip strength of the right hand both at the 2nd week of treatment with Meteospasmyl (increase by 0.4 kg) and by the 4th week of treatment (by 0.6 kg), in contrast with comparison group (F-test ANOVA (2; 60) = 7.2; p=0.0015; Kruskal – Wallis test-H (2; 63) = 27.6161; p=0.00001). The applied method of multivariate analysis of variance with a hypothesis decomposition model confirmed the effect of Meteospasmyl on the increase in the values of hand dynamometry on the 28th day of admission (p trend less than 0.001). The advantages of the presented study are the following characteristics: • New data were obtained on the option of overlapping uninvestigated dyspepsia with nonspecific irritable bowel syndrome. • Patients’ self-assessment of effectiveness in this variant of disorders was not previously studied. • Meteospasmyl demonstrated greater efficiency in comparison with mebeverine and drotaverine. • Meteospasmyl increased the functional state of skeletal muscles. • Meteospasmyl showed a high safety profile.

The combined application of pulsed electromagnetic fields and platelet-rich plasma in the treatment of early-stage knee osteoarthritis: A randomized clinical trial.

This study aims to evaluate the therapeutic efficacy of combined treatment with pulsed electromagnetic fields (PEMFs) and platelet-rich plasma (PRP) injection in improving pain and functional mobility among patients with early-stage knee osteoarthritis (KOA). We hypothesize that this combined therapy can yield superior treatment outcomes. Based on the different treatment regimens, we divided 48 patients diagnosed with Kellgren-Lawrence grades I-III KOA into 3 groups: the PRP group, the PEMFs group, and the PRP + PEMFs group. Each subtype of KOA patients was randomly assigned to different treatment groups. In the PRP group, patients received intra-articular injections of leukocyte-rich platelet-rich plasma once a month for 3 consecutive months. In the PEMFs group, patients receive low-frequency PEMFs irradiation therapy with a frequency of 30 Hz and intensity of 1.5 mT, once daily, 5 times a week, for a consecutive treatment period of 12 weeks. In the PRP + PEMFs group, patients receive both of the aforementioned treatment protocol. The treatment effects on patients are evaluated at baseline and at weeks 4, 8, and 12 post-treatment. Assessment parameters include visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne Index score, and knee joint range of motion. From the 4th to the 12th week of treatment, the visual analog scale scores, Western Ontario and McMaster Universities Osteoarthritis Index scores, and Lequesne index scores of patients in all 3 groups gradually decreased, while knee joint mobility gradually increased (P < .05). At weeks 4, 8, and 12 after treatment, the PRP combined with PEMFs group showed significantly better scores compared to the PRP group and the PEMFs group, with statistically significant differences (P < .05). A total of 7 patients experienced adverse reactions such as knee joint swelling, low-grade fever, and worsening knee joint pain after treatment, all of which disappeared within 1 week after treatment. The incidence of complications did not differ significantly among the 3 groups (P = .67). PRP, PEMFs, and the combination of PRP and PEMFs therapy all effectively alleviate knee joint pain and improve joint function. However, compared to single treatment modalities, the combined therapy of PRP and PEMFs demonstrates more pronounced efficacy.

Effect of adalimumab treatment on inflammatory and hematological parameters in patients with Hidradenitis suppurativa

Objective Hidradenitis suppurativa (HS), a chronic inflammatory disease that typically manifests after puberty, is characterised by painful nodules, abscesses, draining sinus tracts, and scars in areas rich in apocrine glands such as the axillary and inguinal regions. In recent years, blood-based biomarkers such as the Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR), Monocyte/Lymphocyte Ratio (MLR), Mean Platelet Volume (MPV), Systemic Immune-Inflammation Index (SII) and Pan-Immune-Inflammation Value (PIV) have been used as significant indicators of systemic inflammation. While there are few studies evaluating these biomarkers in HS, the response of these markers to treatment has only been assessed in one study to date. Our study aims to investigate the effect of adalimumab treatment on blood-based systemic inflammation biomarkers in HS, where inflammation plays a significant role. Methods The study included 42 adult patients who received adalimumab treatment at our dermatology and venereology clinic between January 2020 and January 2023. Medical records for complete blood count results of the patients were retrospectively reviewed. All systemic inflammation-based biomarkers were calculated from the absolute values of the complete blood count. The SII was calculated with the following formula: (neutrophil count × platelet count/lymphocyte count). The PIV was calculated as follows: (neutrophil count × platelet count × monocyte count/lymphocyte count). Values before the treatment and at the 12th week of treatment were compared. Results When the changes in the inflammatory parameters of the patients were examined, it was found that NLR (2.13 ± 0.87 vs 2.26 ± 1.12), PLR (111.01 ± 39.89 vs 99.43 ± 35.34), MLR (0.27 ± 0.11 vs 0.28 ± 0.12), MPV (9.59 ± 0.71 vs 9.70 ± 0.79), SII (680.79 ± 330.18 vs 687.89 ± 442.66), and PIV (552.02 ± 330.71 vs 605.05 ± 415.96) values did not change statistically significantly after treatment (p > 0.05). While there was a significant decrease in platelet count compared to before treatment, no statistically significant difference was found in the other evaluated blood cells. Conclusion Adalimumab treatment has not had a significant effect on systemic inflammation markers in HS, an inflammatory disease. More studies are needed to evaluate the effect of adalimumab on these markers in HS.

EMDR Flash Technique in adolescents with depression: A twelve-week follow-up study.

This study aims to investigate the specific effects of the EMDR Flash Technique on adolescents with depression. This follow-up study consists of 32 adolescents, 12-17years of age (M = 14.34, SD = 1.56), including 7 males and 25 females. They were evaluated with Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present, the Beck Depression Inventory (BDI), and Children Revised Impact of Event Scale-8 (Crıes-8). These were administered at baseline, at the end of the 4th and 12th weeks of treatment. The EMDR Flash Technique which can be utilized in the preparation phase of Eye Movement Desensitization and Reprocessing (EMDR) to reduce the intensity of highly distressing memories rapidly and relatively painlessly was applied for 12weeks, one session per week as a free-standing intervention. Also, the EMDR Flash Technique can be effective in decreasing the rate of noncompliance and drop-outs of adolescents. The baseline means of total BDI scores decreased from 48.19 to 2.16 at the end of the 12th week of treatment. Also, the CRIES scores decreased from 31.78 to 0.44 at the end of the 12th week of treatment. In addition, the baseline means of SUD scores decreased from 9.53 to zero at the end of the 12th week of treatment. Overall, our results underscore the effectiveness of the EMDR-Flash Technique in adolescents with depression.

EFFECT OF CUPPING THERAPY ON PAIN, CARDIORESPIRATORY PARAMETERS, AND LUNG FUNCTION IN PATIENTS WITH FIBROMYALGIA SYNDROME

Background: The rheumatic condition fibromyalgia syndrome (FMS) is marked by extensive pain, and tender points, with accompanying complaints such as stiffened muscles, depression, anxiety, sleep disturbance, along with dyspnea, exhaustion, and other cardio-respiratory related dysfunction. This study’s goal was to determine the effect of dry cupping intervention on pain, cardiorespiratory parameters as well as lung function in patients with FMS. Methods: Thirty females with FMS (40–60 years old) were enlisted and subsequently divided into two distinct groups: conventional treatment with ([Formula: see text] = 15) and without ([Formula: see text] = 15) cupping therapy i.e. experimental and control groups respectively. All participants received therapies 3 days a week during this study. Visual Analogue Scale (VAS), digital pressure pain threshold (PPT), cardiac parameters including blood pressure using a sphygmomanometer, O2 saturation and pulse rate using a pulse oximeter, respiratory parameters including chest expansion using a measuring tape, lung functions including FVC and FEV1/FVC using a spirometer were used to assess participants on baseline, last day of 2nd and 4th week of treatment. Results: Improvements in pain, PPT, oxygen saturation, pulse rate, and chest expansion, FVC and FEV1/FVC were higher in the group who got cupping therapy including conventional treatment against the group who just received conventional treatment ([Formula: see text] 0.05). At the end of the 4th week, there was no appreciable change in blood pressure levels between the groups ([Formula: see text] 0.05). Conclusion: The FMS treatment plan should include cupping therapy in addition to conventional treatment to help patients improve their cardio-respiratory fitness and overall quality of life.

#1182 Arterial hypertension and chronic obstructive pulmonary disease—problems of choice of therapy

Abstract Background and Aims The development of hypertension in COPD is based on the early formation of endothelial dysfunction in the small and large circulatory circles, increased sympathetic activity with an imbalance in the synthesis of catecholamines, a violation of the role of the lungs in the metabolism of vasoactive substances, oxidative stress, chronic systemic inflammation, an imbalance in the renin-angiotensin-aldosterone system (RAAS). There are few studies confirming the role of RAAS components in the pathogenesis of cardiovascular changes in patients COPD. The activity of angiotensin converting enzyme (ACE) increases with hypoxia, which may play an important role in increasing the degree of systemic hypertension. An increase in the function of the RAAS is possible both under the direct influence of hypoxia and indirectly through activation of the sympathoadrenal system. To evaluate the efficacy and tolerability of the angiotensin II receptor antagonist valsartan (Nortivan) at a dose 80-160 mg per day in patients with hypertension of 1-2 degrees and COPD of stage II-IV. Method The study design is a local, open, incomparable study on the efficacy and safety of the drug Nortivan in patients with hypertension in combination with COPD. We examined 18 patients with stage II-IV in remission, suffering from grade I and II hypertension, determined in accordance with the generally accepted classification of blood pressure levels (VNOK, 2010). Results The criteria for exclusion from the study were the presence in patients of complications of hypertension, coronary heart disease, decompensated chronic pulmonary heart, endocrine diseases requiring drug correction, kidney pathology, chronic heart failure, oral steroid therapy. 10 days in the last 6 months before inclusion in the study, oncological diseases and any other conditions that could interfere with the interpretation and evaluation of the results of the study. Patients who had not previously received antihypertensive treatment were included in the study immediately, and the rest underwent a washing period for 2 weeks. Patients received Nortivan as antihypertensive therapy for 24 weeks. The effectiveness of therapy was controlled by daily monitoring blood pressure. The choice of quality criteria for the effectiveness of therapy parameters SMAD is associated with literature data and own observations on the prevalence of diurnal blood pressure profiles in patients with hypertension and COPD with no decrease or increase in blood pressure at night, when office blood pressure figures are to a lesser extent reflect the effectiveness of antihypertensive therapy. The initial dosage was 80 mg/day. With insufficient hypotensive effect, the dose of the drug was doubled at the 4th week of treatment. The basic COPD therapy did not change throughout the study period and included anticholinergic drugs (ipratropium bromide, tiotropium bromide), beta2-adrenomimetic (fe-noterol) or a combination thereof. Initially and after 24 weeks of treatment, a complete laboratory examination was performed: a clinical blood test, a biochemical blood test. The thickness of the intima-media complex of the carotid arteries and ECG was also studied. The criterion The safety of the therapy was assessed by the indicators of respiratory function, daily pulse oximetry. Conclusion The use of the drug Nortivan has shown high efficacy and safety in patients Grade I–II hypertension in combination with stage II-IV COPD. A statistically and clinically significant normalization of SMAD indicators with correction of pathological types of daily curves due to a decrease in the number of patients with an increase in or the absence of a decrease in blood pressure during the night period. The safety of using the drug in the clinical group with bronchial obstruction syndrome was confirmed by the dynamics of ventilation indicators according to spirometry and the results of daily pulse oximetry, which showed the absence of exacerbation of hypoxia during therapy.

Tokishakuyakusan alleviates ultraviolet-induced skin pigmentation by decreasing the expression of melanogenesis-related enzymes

Ethnopharmacological relevanceTokishakuyakusan (TSS), a traditional Kampo medicine, can effectively alleviate symptoms unique to women, such as menstrual pain and menopausal symptoms, and this effect is believed to be related to its ability to increase the secretion of female hormones. TSS is also believed to be effective against skin pigmentation. However, no studies have examined the effect of TSS on pigmentation. Aim of the studyIn this study, we conducted basic research to determine the effects of TSS on pigmentation. Materials and methodsFemale HRM-2 mice were given free access to a normal diet or a TSS-containing diet for 7 weeks. For 3 weeks starting from the 4th week of treatment, the back of the skin was irradiated with ultraviolet (UV) light, and the melanin level was measured. The expression levels of melanogenesis-related genes and inflammatory markers in the skin were analyzed. ResultsThe melanin level in the skin of the mice exposed to UV radiation was approximately three times greater than that in the skin of the mice in the non-UV-irradiated group, confirming pigmentation due to UV irradiation. The protein expression levels of tyrosinase (Tyr), tyrosinase-related protein-1 (Tyrp1), and dopachrome tautomerase (Dct), which are important for melanin production, were significantly greater in the UV irradiation group than in the non-UV irradiation group. In contrast, the amount of skin melanin in the mice treated with TSS was significantly lower than that in the UV-irradiated group, and the expression levels of melanogenesis-related enzymes were also lower. Furthermore, TSS significantly decreased the expression of microphthalmia transcription factor (Mitf), a transcription factor for melanogenesis-related enzymes, and the inflammatory cytokines interleukin-1β and interleukin-6. ConclusionsTSS inhibits melanin production in melanocytes by suppressing the increase in the expression of melanogenesis-related enzymes caused by UV irradiation. These findings suggested that this effect of TSS is exerted through the combined regulation of MITF expression and anti-inflammatory responses.

Comparative Effect of Augmented Reality and Routine Physical Therapy on Balance and Postural Control in Patients with Parkinson’s disease

Background: Parkinson's disease is a neurodegenerative condition that often manifests in old age with generalized slowness of movements (bradykinesia) and a minimum of one additional symptom of tremor at rest or stiffness. Objective: The purpose is to compare the effects of Augmented Reality and Routine Physical Therapy on balance and Postural Control in Patients with Parkinson's disease. Methodology: It was a randomized clinical trial done in the Neuro medicine and physiotherapy department of Allied Hospital, Faisalabad. A sample size of 62 patients was divided into two equal groups. Patients in Group A had conventional physiotherapy, while those in Group B received augmented reality and conventional physiotherapy. Non probability sampling technique was used. Data was collected on the baseline and then data was collected after 8th weeks, and final data was collected after 12th weeks. Tools for collection of data were the Berg balance scale, timed up and go, and one leg stance test. Results: An Independent sample t-test was used to check the difference between groups in pre and post intervention which shows the statistical difference in both groups after the 8th and 12th weeks of treatment. However, mean differences show that group B has more good results. Repeated measure analysis of variance also shows that there is a significant difference between treatment groups in the within-group analysis. Conclusion: Our study concludes that an augmented reality regimen along with physiotherapy is beneficial for Parkinson’s patients to improve balance and postural control.

Serum Galactomannan as a Minimally Invasive Diagnostic Tool for Fungal Skull Base Osteomyelitis.

Multidrug resistant strains and fungi add to treatment conundrums in skull base osteomyelitis (SBO). Deep tissue culture in these patients is challenging due to their advanced age and co-morbidities. Besides, fungal culture positivity is seen only in 60% of invasive aspergillosis. To determine the efficacy of a minimally invasive test-Serum Galactomannan (sGM)-for diagnosing fungal SBO. Prospective observational study. Thirty- three patients, clinically diagnosed with SBO were included in this study. Baseline ESR (Erythrocyte Sedimentation Rate), CRP (C- Reactive Protein), pain score, and sGM were noted for all patients. Antifungal Voriconazole was initiated on patients if the sGM values were more than 0.8. At the 12th week of treatment, all parameters were repeated and compared with the baseline values. A significant reduction was noted in ESR, CRP, and pain scores at the 12th week of treatment compared to the baseline values in patients with raised sGM values who were started on Voriconazole. For a culture-proven fungal skull base osteomyelitis with a cut-off value of sGM > / = 0.8, the obtained sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 81.82, 36.36, 39.13, 80 and 51.52% respectively. At a cut-off value of sGM > / = 01.6, the values of sensitivity/specificity, PPV, NPV and accuracy were 81.82/72.73%, 60%, 88.89% and 75.76%. Culture-negative patients in SBO with sGM value > 0.8 were more likely to be fungal SBO. An sGM cut-off of 1.6 was observed to give maximum accuracy for diagnosing fungal SBO.

Final conclusions of the own investigations of combined antihypertensive treatment on clinical state in patients with arterial hypertension without and with diabetes mellitus: use of own materials in education in nation. and Engl. languages at pre- and po

General practice – family medicine department. Object of investigation – patients with confirmed diagnosis of arterial hypertension without and with diabetes mellitus of second type, which were under observation at the primary medical care centers. &#x0D; The aim of the investigation was the study of efficiency of the combined (calcium channel blocker – amlodipin besilat and angiotensin II receptor antagonist – valsartan) antihypertensive treatment in patients with arterial hypertension combined with diabetes mellitus from the start of the treatment in the practice of primary care physician.&#x0D; Methods of the investigation included physical examination, general clinical, instrumental and laboratory methods, monitoring of side effects.&#x0D; As a result it was found, that combined antihypertensive treatment (amlodipin and valsartan) is effective and safe in patients with arterial hypertension and diabetes mellitus of 2 type, which helps to reach the target level of arterial pressure in 72 % of patients and can be recommended from the beginning of the treatment in the practice of family physician. Maximal effect of the treatment in patients with arterial hypertension of II-III degree and diabetes mellitus of 2 type was observed only at 12th week of treatment. At combined antihypertensive treatment (amlodipin and valsartan) they observed tendency to the reduction of left ventricle hypertrophy. Despite the rate and percentage of the reaching of target arterial pressure were lower in the group of patients, which have diabetes mellitus of 2 type, it is necessary to recommend more active modification of the way of life in the named group of patients. It was found reduction of heart and vascular risks in the group of patients with arterial hypertension II–III degree with diabetes mellitus 2 type. This makes the basis for more active modification of life style and using from the start of the treatment combined antihypertensive therapy immediately. Consider all found results using from the start of the treatment combined antihypertensive therapy immediately by the primary care physician is proved for patients with arterial hypertension combined with diabetes mellitus.&#x0D; Accumulated materials (including theoretical reviews, demonstrative poster reports etc.) are used at training of interns in speciality «general practice – family medicine», during practical classes for higher courses education in national and English languages

Efficacy and Mechanism of Highly Active Umbilical Cord Mesenchymal Stem Cells in the Treatment of Osteoporosis in Rats.

A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κβ ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, β-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting. The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, β-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment. HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/β-catenin pathway and inhibition of inflammation.</p>.

P700 The efficacy of adalimumab combined with surgery for rectovaginal fistula in Crohn's disease：a single-center retrospective study

Abstract Background To assess the efficacy of adalimumab(ADA)combined with surgery in the treatment of Crohn's disease patients with rectovaginal fistulas. Methods A single-center retrospective study. The baseline data of patients with Crohn’s rectovaginal fistulas who visited the Anorectal Department of the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to July 2022 and accepted ADA combined with surgery treatment were included. Crohn’s disease Activity Index(CDAI), perianal disease activity index(PDAI) and inflammatory parameters, including Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP), were statistically analyzed at weeks0, 48. Follow-up was performed every 8 weeks. The outcomes included clinical response, clinical remission, fistula response, fistula remission, fistula remission under MRI, endoscopic response and endoscopic remission. Results A total of 43 RVF patients were included, 53.4% (23/43) patients were treated with Seton,44.1% (19/43) patients were treated with Advancement flap and 2.3%(1/43) patient was treated with Fecal diversion, with a median follow-up of 11.0 (2.5-15.0) months. After 48 weeks of treatment, CDAI[325(262,397)vs.197(134,396)], PDAI[8(6,9) vs. 5(3,6)], ESR[31(8,50) mm/h vs. 10(4,28)mm/h]and CRP[4.62(0.85, 14.45)mg/L vs.0.5(0.5,2.14)mg/L] were significantly lower than 0 week (Table 1) . CDAI, PDAI, ESR and CRP at the 48th week of treatment were significantly lower than those before treatment (p&amp;lt;0.05). At the last follow-up, 62.7%(27/43) patients achieved clinical response, 30.2%(13/43) achieved clinical remission. Meanwhile 69.7%(30/43) of patients achieved fistula response,32.5%(14/43) achieved fistula remission(Table 2),and 25.5%(11/43) achieved fistula remission under MRI; A total of 37 patients completed endoscopic re-examination, including 54.0% (20/37) of patients with endoscopic response and 24.3%(9/37) with endoscopic remission. Conclusion ADA combined with surgery is effective in the treatment of patients with Crohn’s rectovaginal fistulas.

Effect of Pelvic Radiation on Haematopoeitic and Gastrointestinal Syndromes: a Prospective &amp; Observational Study

Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumor. It has been reported that the majority of patients receiving pelvic radiation therapy show early or late tissue reactions of graded severity as radiotherapy affects not only the targeted tumor cells but also the surrounding healthy tissues. This prospective, observational study was conducted to observe the effects of pelvic radiation on haematopoeitic and gastrointestinal syndromes. It was done in Radiation Oncology department of National Institute of Cancer Research and Hospital, Dhaka between July 2011 to June 2012. The study participants were all patients getting pelvic radiation in the concerned department. A blood profile was done before radiotherapy. Clinical evaluation as per RTOG Guideline was done to access the gastrointestinal syndromes. Then, pelvic radiation was started and CBC was done and recorded weekly as well as gastrointestinal toxicity grading. Main outcome measures were hemoglobin, TC of WBC, nausea, vomiting, diarrhea. Before treatment the mean hemoglobin % was 11.0±1.1 mg/dl, during 4th week of treatment it 10.37±0.7 mg/dl.The mean TC of WBC was found 11107.4±13481.4 mm3, during 4th week of treatment the mean TC of WBC was found 7550.6±2514.6 mm3.Nausea and vomiting increased upto 3rd week but decline in subsequent follow-up. 42% patients had diarrhea during 2ndand 3rd week of treatment, 20.0% in 4thweek and only 2.0% found in 5th week. It can be said that hematopoetic and gastrointestinal syndromes are significantly correlated in patients undergoing pelvic radiation following 4th week of follow up reports. J Bangladesh Coll Phys Surg 2024; 42: 31-37

Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study.

In patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy. The phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination. Between June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation. The study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study. clinicaltrials.gov, ID NCT04050228.

Treatment of Willis-Ekbom Disease (Restless Leg Syndrome); The Efficacy of Mulligan's Traction Straight Leg Raise among Paramedical Professionals.

Background: Restless Leg Syndrome (RLS) is a generalized neurological sensory-motor disorder characterized by intense restlessness and discomfort in the lower extremities, leading to an urge to move the legs at sleep time. Treatment protocols for RLS may include thermotherapy, stretching exercises, and Mulligan’s traction straight leg raise (SLR). Mulligan’s traction SLR is an effective method that influences peripheral and central neural pathways through mobilization, thereby alleviating RLS symptoms. Objective: The study aimed to compare the efficacy of stretching exercises and Mulligan traction straight leg raise in reducing RLS severity among paramedical staff. Methods: This randomized clinical trial included a sample size of 38 paramedical staff members diagnosed with RLS using standard criteria. Participants were allocated using the Convenient Sampling Technique and randomly assigned into Group 1 (Stretching Exercises) and Group 2 (Mulligan Traction SLR) through coin tossing. Each group consisted of 19 participants. The interventions were conducted three times per week for one month. Assessments were made using the RLS Severity Scale, Numeric Pain Rating Scale, Groningen Sleep Quality Scale, and Goniometer at baseline, and after the 2nd and 4th weeks of treatment. Results: The study indicated that both treatments were effective in treating RLS, showing a significant difference with p&lt;0.05. However, Mulligan's TSLR exhibited remarkable results in improving sleep quality, increasing SLR range of both legs, reducing pain intensity, and improving RLS symptoms, with p-values of 0.001, 0.000, 0.012, and 0.001, respectively. Data analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 26. Conclusion: The study concluded that both Stretching Exercises and Mulligan's TSLR are effective treatments for RLS. However, Mulligan's TSLR showed superior effectiveness in reducing pain levels, RLS symptoms, and in improving sleep quality and SLR range among paramedical staff members.

Effects of Low-Level Laser Therapy on Shoulder Pain, Functional Disability and Range of Motion in Patients with Type II Slap Tear

BACKGROUND: Low-level lasers may occasionally replace surgery or medications without adverse effects, so studying them stands to reason. It heals, regenerates tissue, reduces inflammation, discomfort, and boosts immunity. Research is continuing. It may help physical therapy, healthcare, and the community by being cost-efficient, simple, and successful. OBJECTIVE: To compare the effects of low-level laser therapy and routine physical therapy on shoulder pain, functional disability, and range of motion in patients with Type II SLAP tear. METHODS: It was a Randomized Controlled Trial conducted at Physical therapy department, Sialkot Medical and Physiotherapy Center Branches Pasroor and Sambrail. The estimated sample size is 52, and adjusting for an expected 20% dropouts, the sample size was 62, allocated 31 in each group. Both male and female patients with Age between 50-70 years having Type II SLAP tear, Visual analogue scale (VAS) score above 3 and the patients diagnosed by physician, orthopedic physician or surgeon or rheumatologist were included. The included patients were allocated in group A, routine physical therapy, and Group B low level laser. All the patients were assessed at baseline, at 4th week of Treatment and at 8th week of Treatment for pain, shoulder pain and disability index and shoulder ranges. RESULTS: The results regarding age showed mean and standard deviation to be 1.8387±.77875 in routine physical therapy group while 1.8065±.79244 in low level laser therapy group. The comparison of mean SPADI total score at 8th week of assessment it was found to be respectively 58.3226±4.57083 and 50.3871±4.85577 with a significant mean difference of 7.935 in favor of low-level laser therapy as shown by p value 0.000. Other outcome measures including pain and shoulder ranges were also significantly improved in low level laser therapy group, p value &lt; 0.05. CONCUSSION: The findings of the study concluded that low level plays the therapy is significantly more effective improving pain disability and shoulder range of motions in patients with slap tear, except for abduction range of motion which was improved equally in both groups. Moreover, within routine physical therapy and low-level laser therapy group showed significant improvement at pre and post level of assessment except that of total shoulder and pain disability index score which was not improved significantly in routine physical therapy group without combination of low-level laser therapy.

A3 receptor as a target for the treatment of Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease with clinical features including memory loss, cognitive impairment and dementia that affects over six million Americans. Current treatments for AD have limited efficacy due, in part, to the poorly understood multifactorial nature of the mechanisms driving AD. Our data suggests that alteration of adenosine kinase‐dependent adenosine metabolism and inadequate A3 adenosine receptor (A3AR) signaling in the central nervous system (CNS) are key to these processes. The SAMP8 mouse are a mouse model of sporadic AD exhibiting many key characteristics of AD including age‐associated impairment in learning and memory, which corresponds to age‐related increase in beta amyloid, phosphorylated tau, oxidative stress, neuroinflammation, impaired efflux across the blood‐brain barrier and increased regulatory T‐cells in the brain.MethodWe first measured expressions of ADK and A3AR in the hippocampus of 12 month old. SAMP8 mice. We then treated 11 month old SAMP8 mice with MRS5980 an A3AR receptor agonist MLN5980 every other day for 6 weeks. At the end of the 4th week of treatment, behavior tests were conducted for two weeks. Mice were tested in T‐maze, Novel Object Recognition (NORPT), elevated plus maze and open field.Result12 month old SAMP8 mice treated with the A3AR agonist MRS5980 had improved learning and memory in the T‐maze and NORPT compared to the vehicle treated control mice. There was no difference between the young vehicle treated SAMP8 mice and the MRS5980 treated mice. MRS5980 did not affect activity or anxiety in the open field or elevated plus mazes indicating these factors did nor contribute to improvement in learning and memory.ConclusionHere we identify A3AR in key cognitive centers of the brain and its expression increases with cognitive impairment in the SAMP8 AD mouse model. Moreover, adenosine kinase, an enzyme that reduces extracellular adenosine, also increased. We discovered that supplemental A3AR signaling with highly selective, orally bioavailable, CNS‐penetrant A3AR agonists reversed cognitive impairment without any confounding influence on locomotor activity or anxiety. Our results indicate that A3AR is a useful pathway to give additional insight into changes in the brain with AD potential novel therapies.

5-aminolevulinic acid photodynamic therapy using 560-1200 nm followed by 420-1200 nm broadband light in the treatment of moderate-to-severe acne

BackgroundModerate-to-severe acne vulgaris, which is a chronic inflammatory skin disease, seriously impacts millions of people. However, traditional therapies may cause severe adverse reactions that are unacceptable to many patients, thus limiting the further application of these therapies. Novel therapeutic approaches to effectively treat moderate-to-severe acne vulgaris with minimal adverse reactions are urgently needed. In this retrospective study, we investigated the efficacy and adverse reactions of photodynamic therapy (PDT) using 560–1200 nm followed by 420–1200 nm broadband light (BBL). MethodsTwenty-four patients with moderate-to-severe acne vulgaris were included in the study and all patients expressed a strong desire for beauty. After aminolevulinic acid (ALA) gel applied, the entire face was sequentially irradiated by using BBL with a 560 nm cut-off filter (560–1200 nm), followed by BBL with a 420 nm cut-off filter (420–1200 nm). The clinical efficacy was evaluated by the proportion of patients achieving cured response and excellent response (effective rate), based on the percentage of lesions reduction (treatment rate). The fluorescent images and photographs of acne vulgaris were recorded. Pain and other common local adverse reactions during the treatment were also recorded and evaluated. ResultsIn patients with moderate acne, the mean treatment rates were 57.74 ± 16.40 (%) and 87.40 ± 8.521 (%) at the 6th week and 12th week of treatment, respectively. In patients with severe acne, the mean treatment rates were 60.95 ± 12.06 (%) and 85.04 ± 9.115 (%) at the 6th week and 12th week of treatment, respectively. At the 6th and 12th weeks of treatment, the effective rates of patients were 20.00 % and 93.33 % in patients with moderate acne, and 0.000 % and 88.89 % in patients with severe acne, respectively. Pain scores were significantly higher in patients with severe acne compared to patients with moderate acne when receiving 560–1200 nm BBL-PDT. Additionally, patients when receiving 420–1200 nm BBL-PDT exhibited significantly higher pain scores than those when receiving 560–1200 nm BBL-PDT. The degree of erythema was more severe in patients with severe acne than in those with moderate acne. The pigmentation was observed in one patient with moderate acne and one patient with severe acne. ConclusionThe 560–1200 nm and 420–1200 nm BBL-PDT therapy can effectively treat moderate-to-severe acne vulgaris with tolerable adverse reactions, providing a new option for patients with higher esthetic requirements.