Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance.

OBJECTIVES: In this comprehensive study spanning 33 malignancies, we explored the differential expression and prognostic significance of Heparan sulfate 6-O-sulfotransferase 2 (HS6ST2). METHODS: TIMER2, UALCAN, and GEPIA2 were used for the expression analysis. cBioPortal was used for mutational analysis. CancerSEA, STRING, and DAVID, were employed for the single cell sequencing data analysis, protein-protein interaction network development, and gene enrichment analyses, respectively. GSCAlite and RT-qPCR were used for drug sensitivity and expression validation analysis. RESULTS: HS6ST2 exhibited significant (P < 0.05) overexpression in multiple cancers. Prognostically, elevated HS6ST2 expression was significantly associated with poor overall survival (OS) in patients with cervical squamous cell carcinoma (CESC), kidney chromophobe (KICH), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD), emphasizing its potential as a prognostic indicator in these cancers. Moreover, HS6ST2 expression correlated with pathological stages in CESC, KICH, LUAD, and STAD patients. Exploration of genetic alterations using cBioPortal unveiled distinct mutational landscapes, with low mutation frequencies in CESC, KICH, LUAD, and STAD. Additionally, reduced DNA methylation in CESC, KICH, LUAD, and STAD suggested a potential link between hypomethylation and heightened HS6ST2 expression. Analysis of immune cell infiltration revealed a positive correlation between HS6ST2 expression and the infiltration of CD8+ T and CD4+ T cells in CESC, KICH, LUAD, and STAD, highlighting its involvement in the tumor immunology processes. Single-cell functional states analysis demonstrated associations between HS6ST2 and diverse cellular processes. Moreover, gene enrichment analysis revealed the involvement HS6ST2 in crucial cellular activities. GSCAlite analysis underscored the potential of HS6ST2 as a therapeutic target, showing associations with drug sensitivity. Finally, experimental validation through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in LUAD tissues confirmed elevated HS6ST2 expression. CONCLUSION: Overall, this study provides a comprehensive understanding of HS6ST2 in CESC, KICH, LUAD, and STAD, emphasizing its potential as a prognostic biomarker and therapeutic target.

Novel vs. modified platelet-rich plasma therapy for hair loss treatment: a systematic review and meta-analysis.

Platelet-rich plasma (PRP) therapy, is a stand-alone therapy or is used in combination with other treatments for the treatment of androgenic alopecia. The purpose of this meta-analysis was to compare the improvement in hair density seen, when PRP was used alone and when used as an adjunct. Methods: Conforming to systematic review and meta-analysis recommendations, we performed a meta-analysis of relevant articles in multiple databases, from inception till May 2022. Randomized clinical trials were included that evaluated the use of PRP alone or used PRP as an adjuvant with previously used therapies. Hair density data at the start of treatment and follow-up after 3 and 6 months was used for analysis. Results: A review of 255 articles included nine studies, for a cumulative data set of 230 individuals. In comparison to the placebo, stand-alone PRP therapy resulted in a significant increase in hair density (MD=25.39, P<0.00001.) PRP combination therapy also showed marked improvement in hair density compared to placebo (MD=34.38, P=0.002.) When comparing stand-alone PRP to combination therapy, MD=36.16, and MD=34.63 was observed for the two groups, respectively. Conclusions: The results of this meta-analysis reaffirm previous studies that suggest the role of PRP in improving hair density in AGA; however, the results cannot justify the use of PRP-combined therapy. Stand-alone PRP therapy should be considered in the management protocols for both men and women, whereas more studies and may be, different combination therapies are required before combined therapy can be included in the management guidelines for AGA.

Carmustine-Induced Takotsubo Cardiomyopathy.

Carmustine is an intravenous alkylating agent that inhibits DNA synthesis and protein synthesis by forming cross-links in DNA and RNA and ultimately causing cell death. We report a rare case of Takotsubo cardiomyopathy that is thought to be related to carmustine, where the patient presented with chest pain, and ST depression within 12 hours of carmustine therapy. Workup, including echocardiography, showed global hypokinesis of the left ventricle with regional variations; mid and apical anterior septum and apex were akinetic with left ventricular ejection fraction (EF) of 30%. Cardiac catheterization showed nonobstructive coronary artery disease. The patient was treated with a beta-blocker, angiotensin receptor-neprilysin inhibitor (ARNi), and aldosterone receptor antagonists. Two days later, he had a repeat echocardiogram that showed improved EF. After stem cell infusion, his course was complicated with atrial fibrillation with rapid ventricular response and septic shock. Unfortunately, he suffered a cardiac arrest and expired. Carmustine-related cardiomyopathy seems to be very rare, and, to our knowledge, this is the first case report.

Effects of motivational interviewing with conventional physical therapy on rehabilitation of chronic musculoskeletal disorders: A quasi-experimental study.

OBJECTIVE: To compare the effects of motivational interviewing with conventional physical therapy in the rehabilitation of chronic musculoskeletal disorders compared to conventional physical therapy alone. METHODS: The quasi-experimental study was conducted from September 2017 to March 2018 after approval from the University of Health Sciences, Lahore, Pakistan, and comprised patients with chronic musculoskeletal disorders enrolled from various outpatient physical therapy clinics in Lahore. The subjects were alternatively allocated to intervention group A and control group B, with the former receiving motivational interviewing along with conventional physical therapy, and the latter receiving conventional physical therapy alone. The effects of the intervention were measured using visual analogue scale, patient-specific functional scale and exercise compliance chart with two-week follow-up. Data was analysed using SPSS 21. RESULTS: Of the 96 subjects, there were 48(50%) in each of the two groups. There were 21(44%) males and 27(56%) females in group A with a mean age of 50.10±10.35 years, and 23(48%) males and 25(52%) females in group B with a mean age of 50.18±11.58 years. Pain score and functional status were significantly better in group A compared to group B from the baseline to day 14 (p<0.001). Exercise compliance was significantly different between the groups (p<0.001). Intra-group effects of pain intensity, functional status and exercise compliance were also significant (p<0.001). CONCLUSION: Integration of motivational interviewing with conventional physical therapy was found to decrease pain and functional limitations and improve exercise compliance.

Atypical Presentation of Pulmonary Embolism Several Months After COVID-19 Infection.

A 47-year-old female with a past medical history of morbid obesity and hypertension presented with acute onset dizziness that started while she was at work one evening. She did not have chest pain or dyspnea. She had vital signs within an acceptable range, oxygen saturation of 98%-99%, and was not in acute distress. Examination including the Dix-Hallpike maneuver was unremarkable. Computed tomography angiography (CTA) of the head and neck disclosed bilateral pulmonary embolism without any evidence of cerebral ischemia. CTA chest confirmed the diagnosis of bilateral pulmonary emboli. Importantly, besides the obesity, the patient did not have any other risk factors of pulmonary embolism including recent immobilization, surgery, hormonal therapy or contraceptive use, and personal or family history of thromboembolic disorders. However, she was diagnosed with COVID-19 infection six months back with symptoms not requiring hospitalization. Following further workup for her dizziness and neurology evaluation, in the absence of any other plausible etiology, her presenting symptom was attributed to the atypical presentation of pulmonary embolism. She was treated with heparin in the hospital and discharged on apixaban. Her symptoms had resolved at the time of discharge.

Prevalence and treatment of neurological and psychiatric disorders among tertiary hospitals in Pakistan; findings and implications.

INTRODUCTION: Mental health and neurological disorders are prevalent in Pakistan. However, there are considerable concerns with their management due to issues of access, availability of trained personnel and stigma alongside paucity of such data. Consequently, there is a need to document current treatment approaches starting with tertiary hospitals in Pakistan where patients with more severe mental and neurological disorders are typically treated. Subsequently, use the findings to help direct future policies and initiatives. METHODS: Multi-centered, cross-sectional, prospective study principally evaluating current medicine usage among patients attending tertiary hospitals in Pakistan with psychiatric and neurological disorders. In addition, possible factors contributing to the prevalence of these disorders in this population to help with future care. All 23 tertiary care hospitals in the ten major Districts in Pakistan were included, which cover 75% of the population. RESULTS: 57,664 patients were evaluated of which 35.3% were females. Both females and males had multiple brain disorders and multiple co-morbidities. Schizophrenia was the most prevalent disorder overall among both females (25.2%) and males (30.4%). A median of six medicines were prescribed per patient, with antipsychotics and antidepressants the most prescribed medicines. Clozapine was the most prescribed medicine in males (12.25%) and females (11.83%) including for psychiatric disorders, with sodium valproate the most prescribed medicine in epilepsy in males (42.44% of all anti-epileptic medicines) as well as females (46.38%). There was a greater prevalence of both disorders among the lower classes. A greater prevalence of schizophrenia was seen in patients abusing alcohol and smokers. The divorce rate was higher among the studied patients and the prevalence of depression was higher among the widowed population. CONCLUSIONS: There were concerns with the quality of prescribing including the extent of polypharmacy as well as possible overuse of clozapine especially in patients with epilepsy, both of which need addressing.

Transcranial Magnetic Stimulation as a Therapeutic Option for Neurologic and Psychiatric Illnesses.

In recent years, transcranial magnetic stimulation has become an area of interest in the field of neurosciences due to its ability to non-invasively induce sufficient electric current to depolarize superficial axons and networks in the cortex and can be used to explore brain functioning. Evidence shows that transcranial magnetic stimulation could be used as a diagnostic and therapeutic tool for various neurological and psychiatric illnesses. The aim of this review is to introduce the basics of this technology to the readers and to bring together an overview of some of its clinical applications investigated thus far.

Spasmogenic and spasmolytic activity of rind of Punica granatum Linn.

BACKGROUND: Rind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range. METHODS: Rind of Punica granatum was subjected to shade drying. Shade dried materials were pulverized using conventional grinder. Grinded materials were macerated in commercial grade methanol. The extract of rind of P. granatum was concentrated using a rotary evaporator. Rabbits' jejunal preparations were mounted in organ bath containing 10 ml Tyrode's solution, constantly aerated with carbogen gas. Pg. Cr was tested on spontaneous rabbits' jejunal preparations in concentrations 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml. Pg. Cr was also tested on KCl (80 mM)-induced contractions in rabbits' jejunal preparations. Since we observed spasmogenic activity for the first time, hence we also determined the effects of Pg. Cr in presence of atropine (0.03 µM). Pg. Cr was also tested in presence of 0.03 µM of loratadine HCl. Pg. Cr was also tested on barium chloride induced contractions. Calcium Concentration Response Curves (CCRCs) were constructed in the absence and presence of test samples of Pg. Cr in decalcified tissues to explore its possible mode of action. Acute toxicity screening was also performed to determine its safe dose range. RESULTS: Phytochemical screening revealed the presence of saponins, tannins, carbohydrates, proteins, flavonoids, saponins and steroids. However, Pg. Cr tested negative for alkaloids and triterpenoids. Pg. Cr was safe up to 100 mg/kg with its LD50 = 1305 mg/kg. Its respective EC50, in the absence and presence of atropine, were 9.7 ± 0.3 and 3.12 ± 0.45 mg/ml. In the presence of 0.02 and 0.08 µM of loratadine HCl, respective EC50 were 5.6 ± 0.4 and 2.8 ± 0.15 mg/ml. EC50 for relaxant effects on KCl-induced contractions was 8.6 ± 1 mg/ml. In the presence of 0.3 mg/ml of Pg. Cr, a right shift was observed with EC50 (log [Ca++]M) = -1.8 ± 0.09 vs. control EC50 -2.6 ± 0.01. Similarly, EC50 for verapamil (0.1 µM) was -2.4 ± 0.011vs. control EC50= -2.4 ± 0.01. The right shift of P. granatum resembled the right shift of verapamil suggesting for inhibition of voltage gated calcium channels. CONCLUSIONS: P. granatum is safe up to 100 mg/kg. In low concentrations, P. granatum produced spasmogenic activity possibly through involvement of cholinergic and histaminergic receptors. The spasmolytic action may follow inhibition of the voltage gated calcium channels.

Parasiticidal and brine shrimp cytotoxicity potential of crude methanolic extract of rind of Punica granatum Linn against round worms and tape worms.

Rind of Punica granatum is traditionally used for anthelmintic purposes. The current work describes the possible anthelmintic activity of crude methanolic extract of Punica granatum (Pg. Cr) against round worms (Ascaridia galli) and the tape worms (Raillietina spiralis). Brine shrimp cytotoxicity is also performed. Brine shrimp cytotoxic activity was tested using different concentrations (1000 µg/mL, 100 µg/mL and 10 µg/mL) of Pg.Cr. In vitro anthelmintic activity of Pg. Cr was determined against the parasites using albendazole and piperazine citrate as standard anthelmintic drugs in concentration 10 mg/ml. LC50 value for Brine shrimp cytotoxicity was 189.44 ±28 µg/mL. In test concentration of 40mg/ml of the Pg. Cr, Raillietina spiralis was paralyzed in 23 minutes. However, for parasiticidal activity (death of the parasite), it took less time (40 minutes) as compared to standard Albendazole. Time taken for death of the parasite Raillietina spiralis, in concentration 40 mg /ml, is 40 min. While standard drugs took more time to kill the Raillietina spiralis. Pg. Cr took 19 minutes to paralyze the Ascaridia galli at concentration 40 mg/ml whereas; it took 48 minutes for to kill the parasite Ascaridia galli. The current work confirms the traditional use of rind of Punica granatum as anthelmintic against Raillietina spiralis and Ascaridia galli. Results of brine shrimp cytotoxicity assay warrant for the isolation of cytotoxic compounds. List of abbreviation- Pg. Cr = Crude methanolic extract of Punica granatum.

Narrow emission linewidths of positioned InAs quantum dots grown on pre-patterned GaAs(100) substrates.

We report photoluminescence measurements on a single layer of site-controlled InAs quantum dots (QDs) grown by molecular beam epitaxy (MBE) on pre-patterned GaAs(100) substrates with a 15 nm re-growth buffer separating the dots from the re-growth interface. A process for cleaning the re-growth interface allows us to measure single dot emission linewidths of 80 µeV under non-resonant optical excitation, similar to that observed for self-assembled QDs. The dots reveal excitonic transitions confirmed by power dependence and fine structure splitting measurements. The emission wavelengths are stable, which indicates the absence of a fluctuating charge background in the sample and confirms the cleanliness of the re-growth interface.