MaxiK channel partners: physiological impact

The basic functional unit of the large-conductance, voltage- and Ca²⁺-activated K⁺ (MaxiK, BK, BK_Ca) channel is a tetramer of the pore-forming α-subunit (MaxiKα) encoded by a single gene, Slo , holding multiple alternative exons. Depending on the tissue, MaxiKα can associate with modulatory β-subunits (β1–β4) increasing its functional diversity. As MaxiK senses and regulates membrane voltage and intracellular Ca²⁺, it links cell excitability with cell signalling and metabolism. Thus, MaxiK is a key regulator of vital body functions, like blood flow, uresis, immunity and neurotransmission. Epilepsy with paroxysmal dyskinesia syndrome has been recognized as a MaxiKα-related disorder caused by a gain-of-function C-terminus mutation. This channel region is also emerging as a key recognition module containing sequences for MaxiKα interaction with its surrounding signalling partners, and its targeting to cell-specific microdomains. The growing list of interacting proteins highlights the possibility that associations with the C-terminus of MaxiKα are dynamic and depending on each cellular environment. We speculate that the molecular multiplicity of the C-terminus (and intracellular loops) dictated by alternative exons may modulate or create additional interacting sites in a tissue-specific manner. A challenge is the dissection of MaxiK macromolecular signalling complexes in different tissues and their temporal association/dissociation according to the stimulus.     

The influence of laser frequency and groove distance on cell adhesion,cell viability,and antibacterial characteristics of Ti-6Al-4V dental implants treated by modern fiber engraving laser

ObjectiveMicro-nano scale surface modification of Ti-6Al-4V was investigated through the fascinated modern fiber engraving laser method. The process was performed at a high laser speed of 2000 mm/s, under different laser frequencies (20–160 kHz) and groove distances (0.5–50 μm).MethodsTopographic evaluations such as Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscopy (FE-SEM) were used to identify the quality and regularity of patterns. The proliferation of human osteoblast-like osteosarcoma cells (MG63) was analyzed by MTT assay for up to 72 h. Also, the plate counting method was used to quantify the viability potential of the modified surface against Escherichia coli bacteria.ResultsThe cellular viability of the sample modified at the laser frequency of 20 kHz and grooving distance of 50 μm increased up to 35 and 10% compared to the non-treated and control samples, respectively. In the case of the surface modification at lower grooving distances range between 0.5–50 μm, the maximum laser frequency (160 kHz) applied leads to lower pulse’s energies and less bacterial adhesion. Otherwise, at groove distances more than 50 μm, the minimum laser frequency (20 kHz) applied reduces the laser pulse overlaps, increases the cell adhesion and antibacterial properties.SignificanceSurface modification by the fiber engraving laser process significantly enhances the cell adhesion on the surface. As a result of such roughness and cell adhesion enhancement, the surface toxicity feature diminished, and its antibacterial properties improved.     

The effects of concurrent training (aerobic-resistance) and milk consumption on some markers of bone mineral density in women with osteoporosis

Background

Osteoporosis is a skeletal metabolic disorder characterized by low bone mineral density (BMD) and reduced bone strength leading to higher bone fractures risk. The present study attempted to investigate the effects of concurrent training (aerobic-resistance) and milk consumption on some markers of BMD in women with osteoporosis.

Methods

For this purpose, forty women diagnosed with osteoporosis within an age range of 30-45?years were divided into four groups of ten including concurrent training-milk, concurrent training, milk consumption and control group. The concurrent exercises were performed in ten weeks with three sessions in each week including aerobic training (running at 55–75% of maximum heart rate) and resistance training (4 move in a circle performed two times with 10 repetition maximum (RM)). Milk consumption was two times of 250?ml per day in ten weeks. Before and after treatment, BMDs in the hip and lumbar spine area were estimated with Dual-energy X-ray absorptiometry (DEXA) device and 5?cc blood was taken from a vein in the arm to determine the blood levels of 25-hydroxyvitamin D (25OH-D) and alkaline phosphatase (ALP).

Results

Based on the results, blood levels 25OH-D and ALP significantly increased in concurrent training-milk, concurrent training and milk group with higher increase in concurrent training-milk group (P?<?0.05). Furthermore, the right and left hip BMD in concurrent training-milk and concurrent training groups increased significantly with higher increase in concurrent training-milk group (p?<?0.05). Also, lumbar spine BMD increased significantly in concurrent training-milk and concurrent training (p?<?0.05).

Conclusions

It seems that combination of concurrent training and milk consumption has more efficient impacts on the BMD of young women diagnosed with osteoporosis compared to the milk or concurrent training groups alone. This treatment can be used as an effective way to improve BMD in young women with diagnosed osteoporosis.

     

Selenium Deficiency After Bariatric Surgery,Incidence and Symptoms: a Systematic Review and Meta-Analysis

Obesity Surgery - This study review the prevalence of selenium deficiency after bariatric surgery, incidence, and symptoms.&nbsp;A systematic literature search and meta-analysis was performed...     

Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myélome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.      

Predictors of Weight Regain and Insufficient Weight Loss According to Different Definitions After Sleeve Gastrectomy: a Retrospective Analytical Study

Background

Weight regain (WR) and insufficient weight loss (IWL) after sleeve gastrectomy (SG) are challenging issues. This study aimed to evaluate the predictors of WR and IWL after SG.

Methods

In this retrospective analytical study, 568 patients who underwent SG at Hazrat-e Rasool General Hospital, Tehran, Iran, between January 2015 and April 2022 were evaluated. A total of 333 patients were included. WR and IWL were evaluated by multiple criteria such as a BMI of > 35 kg/m², an increase in BMI of > 5 kg/m² above nadir, an increase in weight of > 10 kg above nadir, percentage of excess weight loss (%EWL) < 50% at 18 months, an increase in weight of > 25% of EWL from nadir at 36 months, and percentage of total weight loss (%TWL) < 20% at 36 months. All participants were followed up for 36 months.

Result

The univariate analysis showed that preoperative BMI, obstructive sleep apnea, metformin consumption, and grades 2 and 3 fatty liver disease were associated with WR and IWL (P < 0.05). WR or IWL incidence varied (0–19.3%) based on different definitions. The multivariate analysis showed that a preoperative BMI of > 45 kg/m² [odds ratio_Adjusted (OR_Adj) 1.77, 95% CI: 1.12–4.11, P = 0.038] and metformin consumption [OR_Adj: 0.48, 95% CI: 0.19–0.78, P = 0.001] were associated with WR and IWL after SG, regardless of the definition of WR or IWL.

Conclusion

This study showed that preoperative BMI of > 45 kg/m², obstructive sleep apnea, metformin consumption, and grades 2 and 3 of fatty liver disease were associated with WR or IWL.

Graphical abstract

     

Current treatment of Hodgkin's disease

In spite of the fact that Hodgkin's disease (HD) remains still an enigma its management and treatment yield a cure rate of about 80% of all patients. However, this management has two limits: on one side favourable cases which should not be overtreated because of unacceptable side-effects, and on the other side very unfavourable cases which should be treated differently because of a very high rate of failure and/or relapse. Then it becomes necessary to precise as thoroughly as possible these two limits in order to choose the adequate treatment for the patient. Prognostic factors based on patient and disease characteristics allow a relatively exact classification of favourable and unfavourable cases. This distinction in two prognostic groups has therapeutic implications in terms of chemotherapy (regimen, duration) and radiotherapy (extension, doses). Other specific situations have to be considered, e.g. pediatric cases, pregnancy, old age and HIV-infected patients who need an adapted management according to very different situations.     

Cardiac and Renal Malformations in a Patient with Sepsis and Severe Congenital Neutropenia

Background

G6PC3 deficiency is a new neutropenic syndrome, which is characterized by severe persistent neutropenia, early onset infections and additional organ involvement, especially cardiac and urogenital malformations.

Case Presentation

In this report, we present the clinical details of a recently known case of severe congenital neutropenia (SCN) with G6PC3 mutation, who experienced the first episode of infections at birth. Repeated absolute neutrophil count of less than 500/µl was detected during work-up of sepsis in the first month of life. SCN was diagnosed and granulocyte colony-stimulating factor (GCSF) administration initiated. Bone marrow examination revealed maturation arrest in myeloid series at promyelocyte-myelocyte stage. Diarrhea, bronchiolitis, and urinary tract infection were other infectious complications, while hydronephrosis, atrial septal defect, and patent ductus arteriosus were other manifestations.

Conclusion

Prompt and accurate diagnosis of neutropenic patients and appropriate treatment can prevent further complications and improve the quality of life of the affected patients.