Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa

Methods: A finite element model of the upper cervical spine was developed. A type II dens fracture was induced in the intact model to produce the injured model. The following three constructs were simulated on the intact and injured models: transarticular screw (C1– C2TA), lateral mass screw in C1 and pedicle screw in C2 (C1LM1–C2PD), and lateral mass screw in C1 and translaminar screw in C2 (C1LM1–C2TL). Results: In the intact model, flexion–extension range of motion (ROM) was reduced by up to 99% with C11–C2TA and 98% with C1LM1–C2PD and C1LM1–C2TL. The lateral bending ROM in the intact model was reduced by 100%, 95%, and 75% with C11–C2TA, C1LM1–C2PD, and C1LM1–C2TL, respectively. The axial rotation ROM in the intact model was reduced by 99%, 98%, and 99% with C11–C2TA, C1LM1–C2PD, and C1LM1–C2TL, respectively. The largest maximum von Mises stress was predicted for C1LM1–C2TL (332 MPa) followed by C1LM1–C2PD (307 MPa) and C11–C2TA (133 MPa). Maximum stress was predicted to be at the lateral mass screw head of the C1LM1–C2TL construct. Conclusions Our model indicates that the biomechanical stability of the atlantoaxial joint in lateral bending with translaminar screws is not as reliable as that with transarticular and pedicle screws. Translaminar screws experience large stresses that may lead to failure of the construct before the required bony fusion occurs.

The well-known detrimental effects of cadmium (Cd) on plants are chloroplast destruction, photosynthetic pigment inhibition, imbalance of essential plant nutrients, and membrane damage. Jasmonic acid (JA) is an alleviator against different stresses such as salinity and drought. However, the functional attributes of JA in plants such as the interactive effects of JA application and Cd on rapeseed in response to heavy metal stress remain unclear. JA at 50 µmol/L was observed in literature to have senescence effects in plants. In the present study, 25 µmol/L JA is observed to be a "stress ameliorating molecule" by improving the tolerance of rapeseed plants to Cd toxicity. JA reduces the Cd uptake in the leaves, thereby reducing membrane damage and malondialdehyde content and increasing the essential nutrient uptake. Furthermore, JA shields the chloroplast against the damaging effects of Cd, thereby increasing gas exchange and photosynthetic pigments. Moreover, JA modulates the antioxidant enzyme activity to strengthen the internal defense system. Our results demonstrate the function of JA in alleviating Cd toxicity and its underlying mechanism. Moreover, JA attenuates the damage of Cd to plants. This study enriches our knowledge regarding the use of and protection provided by JA in Cd stress.
Brassica napus/metabolism* ; Cadmium/toxicity* ; Catalase/metabolism* ; Cyclopentanes/pharmacology* ; Oxylipins/pharmacology* ; Photosynthesis ; Plant Leaves/metabolism* ; Superoxide Dismutase/metabolism*

PURPOSE: Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the same inhaler device versus mixed device types for asthma controller and reliever therapy. METHODS: This retrospective observational study identified patients with asthma (ages 4-80 years) in a large primary care database who were prescribed an inhaled corticosteroid (ICS) for the first time. We compared outcomes for patients prescribed the same breath-actuated inhaler (BAI) for ICS controller and salbutamol reliever versus mixed devices (BAI for controller and pressurised metered-dose inhaler [pMDI] for reliever). The 2-year study included 1 baseline year before the ICS prescription (to identify and correct for confounding factors) and 1 outcome year. Endpoints were asthma control (defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and severe exacerbations (hospitalisation or oral corticosteroids for asthma). RESULTS: Patients prescribed the same device (n=3,428) were significantly more likely to achieve asthma control (adjusted odds ratio, 1.15; 95% confidence interval [CI], 1.02-1.28) and recorded significantly lower severe exacerbation rates (adjusted rate ratio, 0.79; 95% CI, 0.68-0.93) than those prescribed mixed devices (n=5,452). CONCLUSIONS: These findings suggest that, when possible, the same device should be prescribed for both ICS and reliever therapy when patients are initiating ICS.
Adrenal Cortex Hormones ; Albuterol ; Anti-Bacterial Agents ; Asthma ; Humans ; Inhalation ; Nebulizers and Vaporizers ; Odds Ratio ; Prescriptions ; Primary Health Care ; Respiratory System ; Retrospective Studies