Illness anxiety, infertility stress, resilience and thyroid-stimulating hormone among infertile people undergoing ART treatment in China.

OBJECTIVE: Infertile people undergoing assisted reproductive technology (ART) treatment in China may experience severe infertility-related stress and illness anxiety (IA). However, little relevant research has been conducted until now. DESIGN: This study investigated the IA of 340 infertile people undergoing ART treatment, including 43 males, 292 females and 5 who preferred not to answer, in 2 tertiary general public hospitals in Wen Zhou, China. MAIN OUTCOME MEASURES: Blood samples for thyroid-stimulating hormone (TSH) levels were obtained from 107 women to explore the relationship between IA and TSH. The questionnaire contained the Mandarin version of the Fertility Problem Inventory, the Resilient Trait Scale for Chinese Adults and the Whiteley Index, measuring infertility stress, resilience and IA, respectively. RESULTS: An incidence rate of 44.1% of IA among infertile people undergoing ART treatment in China was determined, and 30.2% of men and 46.6% of women had severe IA (χ2 = 4.05, p < 0.05). The risk of severe IA in women was around twice that in men (OR = 2.01, 95% CI: 1.01-4.01). Women's IA level was significantly associated with their TSH level (ß = 0.27, p < 0.01). Resilience played a moderating role in the relationship between parenthood importance and illness anxiety. CONCLUSION: This study highlighted the importance and urgency of providing holistic care for illness anxiety of infertile people undergoing ART treatment in China, especially women. The findings of this study indicated that mind-body therapies and resilience empowerment workshops could be conducive to infertile people's holistic health.

Knockdown of Chk1 inhibits proliferation and promotes apoptosis in mouse granulosa cells and its regulation mechanism by miR-15a and miR-16.

Checkpoint kinase 1 (Chk1) is a protein kinase which preserves the genome integrity, and works as an evolutionally conserved DNA damage response and cell cycle checkpoint. However, the functional roles and regulatory mechanism of Chk1 in mouse granulosa cells (GCs) have not been fully elucidated. In this study, by RNA interfering, Chk1 gene was knocked down in GCs. Knockdown of Chk1 inhibited proliferation and increased apoptosis of GCs (p < 0.05), respectively; in addition, cell cycle of GCs was arrested at S and G2/M phases. Further qRT-PCR results showed that cell cycle factors (Cyclin B1 and Cyclin D 1) and a marker gene of proliferation (PCNA) were downregulated (p < 0.001), while apoptotic factors (p53b, p21, caspase-3, and Bax) were upregulated (p < 0.01), which suggested that knockdown of Chk1 may inhibit proliferation, regulate cell cycle, and promote apoptosis at the transcriptional level in GCs. In vitro studies showed a negative correlation between Chk1 mRNA and miR-16 expression during follicular development. To elucidate the relationship between Chk1 and miR-15a/16, luciferase reporter plasmids were constructed and luciferase assays revealed that both miR-15a and miR-16 could bind to the 3' UTR of Chk1 mRNA, and significantly downregulate the protein level of Chk1 (p < 0.01), while miR-16, not miR-15a, could significantly decrease the mRNA level of Chk1 (p < 0.05). This result indicated that miR-16 directly induced Chk1 mRNA destabilization, while miR-15a regulated Chk1 expression through translational repression. Taken together, this study uncovered the roles of Chk1 in mouse granulosa cells and its regulation by miR-15a and miR-16 through different mechanisms.

The Association Between Internet Addiction and Anxiety in Nursing Students: A Network Analysis.

Background: Nursing students who suffer from co-occurring anxiety experience added difficulties when communicating and interacting with others in a healthy, positive, and meaningful way. Previous studies have found strong positive correlations between Internet addiction (IA) and anxiety, suggesting that nursing students who report severe IA are susceptible to debilitating anxiety as well. To date, however, network analysis (NA) studies exploring the nature of association between individual symptoms of IA and anxiety have not been published. Objective: This study examined associations between symptoms of IA and anxiety among nursing students using network analysis. Methods: IA and anxiety symptoms were assessed using the Internet Addiction Test (IAT) and the Generalized Anxiety Disorder Screener (GAD-7), respectively. The structure of IA and anxiety symptoms was characterized using "Strength" as a centrality index in the symptom network. Network stability was tested using a case-dropping bootstrap procedure and a Network Comparison Test (NCT) was conducted to examine whether network characteristics differed on the basis of gender and by region of residence. Results: A total of 1,070 nursing students participated in the study. Network analysis showed that IAT nodes, "Academic decline due to Internet use," "Depressed/moody/nervous only while being off-line," "School grades suffer due to Internet use," and "Others complain about your time spent online" were the most influential symptoms in the IA-anxiety network model. Gender and urban/rural residence did not significantly influence the overall network structure. Conclusion: Several influential individual symptoms including Academic declines due to Internet use, Depressed/moody/nervous only while being off-line, School grades suffering due to Internet use and Others complain about one's time spent online emerged as potential targets for clinical interventions to reduce co-occurring IA and anxiety. Additionally, the overall network structure provides a data-based hypothesis for explaining potential mechanisms that account for comorbid IA and anxiety.

Prevalence of problematic Internet use and its association with quality of life among undergraduate nursing students in the later stage of COVID-19 pandemic era in China.

BACKGROUND AND OBJECTIVES: The prevalence of problematic Internet use (PIU) in the post-COVID-19 pandemic era is not known. This cross-sectional study aimed to determine the prevalence of PIU among baccalaureate nursing students (hereafter: nursing students) in the post-COVID-19 era. METHODS: A total of 1070 nursing students were consecutively invited to participate in this study from the nursing schools of five universities. PIU and quality of life (QOL) were assessed using the Internet Addiction Test (IAT) and the World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF), respectively. t Tests, χ2 , tests, and Kruskal-Wallis tests were used to compare basic demographic and clinical characteristics between participants with and without PIU. Binary logistic regression analysis was used to examine independent correlates. RESULTS: The prevalence of PIU was 23.3% (95% confidence interval [CI]: 20.7%-25.8%). Multiple logistic regression analysis revealed that second- (p = .024) and third-year (p = .012) students were more likely to suffer from PIU compared with first year students. Students with more severe depressive (p = .014) and anxiety symptoms (p = .011) were independently and significantly associated with more severe PIU. After controlling for covariates, nursing students with PIU had a lower overall QOL score (p = .002). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Problematic Internet use (PIU) was common among nursing students in the post-COVID-19 era. Considering the negative impact of PIU on QOL and academic performance, regular screening should be conducted and effective interventions implemented for nursing students with PIU. This was the first study on the prevalence of PIU among nursing students in the post-COVID-19 era. The findings of this study could help health professionals and education authorities to understand the patterns of PIU and its influence on QOL among nursing students and to allocate health resources and develop effective measures to reduce the risk of PIU in this population.

Network analysis of anxiety and depressive symptoms among nursing students during the COVID-19 pandemic.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic has impacted the mental health and well-being of medical personnel, including nursing students. Network analysis provides a deeper characterization of symptom-symptom interactions in mental disorders. The aim of this study was to elucidate characteristics of anxiety and depressive symptom networks of Chinese nursing students during the COVID-19 pandemic. METHOD: A total of 932 nursing students were included. Anxiety and depressive symptom were measured using the seven-item Generalized Anxiety Disorder Scale (GAD-7) and two-item Patient Health Questionnaire (PHQ-2), respectively. Central symptoms and bridge symptoms were identified via centrality indices and bridge centrality indices, respectively. Network stability was examined using the case-dropping procedure. RESULTS: Irritability, Uncontrollable worry, Trouble relaxing, and Depressed mood had the highest centrality values. Three bridge symptoms (Depressed mood, Nervousness, and Anhedonia) were also identified. Neither gender nor region of residence was associated with network global strength, distribution of edge weights or individual edge weights. LIMITATIONS: Data were collected in a cross-sectional study design, therefore, causal relations and dynamic changes between anxiety and depressive symptoms over time could not be inferred. Generalizability of findings may be limited to Chinese nursing students during a particular phase of the current pandemic. CONCLUSIONS: Irritability, Uncontrollable worry, Trouble relaxing, and Depressed mood constituted central symptoms maintaining the anxiety-depression network structure of Chinese nursing students during the pandemic. Timely, systemic multi-level interventions targeting central symptoms and bridge symptoms may be effective in alleviating co-occurring experiences of anxiety and depression in this population.

The prevalence of fatigue among Chinese nursing students in post-COVID-19 era.

BACKGROUND: Due to the COVID-19 outbreak, all teaching activities in nursing schools were suspended in China, and many nursing students were summoned to work in hospitals to compensate for the shortage of manpower. This study examined the prevalence of fatigue and its association with quality of life (QOL) among nursing students during the post-COVID-19 era in China. METHODS: This was a multicenter, cross-sectional study. Nursing students in five Chinese universities were invited to participate. Fatigue, depressive and anxiety symptoms, pain and QOL were measured using standardized instruments. RESULTS: A total of 1,070 nursing students participated. The prevalence of fatigue was 67.3% (95% CI [64.4-70.0]). Multiple logistic regression analysis revealed that male gender (P = 0.003, OR = 1.73, 95% CI [1.20-2.49]), and being a senior nursing student (second year: OR = 2.20, 95% CI [1.46-3.33], P < 0.001; third year: OR = 3.53, 95% CI [2.31-5.41], P < 0.001; and fourth year OR = 3.59, 95% CI [2.39-5.40], P < 0.001) were significantly associated with more severe fatigue. In addition, moderate economic loss during the COVID-19 pandemic (OR = 1.48, 95% CI [1.08-3.33], P < 0.015; compared to low loss), participants with more severe depressive (OR = 1.48, 95% CI [1.22-1.78], P < 0.001) and anxiety symptoms (OR = 1.12, 95% CI [1.05-1.20], P = 0.001), and more severe pain (OR = 1.67, 95%CI [1.46-1.91], P < 0.001) were significantly associated with reported more severe fatigue. After controlling for covariates, nursing students with fatigue had a lower overall QOL score compared to those without (F (1, 1070) = 31.4, P < 0.001). CONCLUSION: Fatigue was common among nursing students in the post-COVID-19 era. Considering the negative impact of fatigue on QOL and daily functioning, routine physical and mental health screening should be conducted for nursing students. Effective stress-reduction measures should be enforced to assist this subpopulation to combat fatigue and restore optimal health.

Changes in Nursing Students' Career Choices Following the COVID-19 Pandemic in China.

Background: Health professionals including nurses have experienced heavy workload and great physical and mental health challenges during the coronavirus disease 19 (COVID-19) pandemic, which may affect nursing students' career choices. This study examined the changes in nursing students' career choices after the onset of the COVID-19 pandemic in China. Methods: This study was conducted in five University nursing schools in China between September 14, 2020 and October 7, 2020. Career choices before and after the COVID-19 pandemic were collected and analyzed. Results: In total, 1,070 nursing students participated in the study. The reported choice of nursing as future career increased from 50.9% [95% confidence interval (CI): 47.9-53.9%] before the COVID-19 pandemic to 62.7% (95%CI: 59.8-65.6%) after the onset of COVID-19 pandemic. Students who chose nursing as their future career following the COVID-19 outbreak had less severe depression and anxiety compared to those who did not choose nursing, but the associations of depression and anxiety with career choice disappeared in multivariable analyses. Binary logistic regression analysis revealed that male gender [odds ratio (OR) = 0.68, 95% CI: 0.50-0.91], rural residence (OR = 1.53, 95%CI: 1.17-2.00), fourth year students (OR = 0.50, 95%CI: 0.35-0.72), negative experiences during the COVID-19 pandemic (OR = 0.66, 95%CI: 0.47-0.92), and good health (OR = 4.6, 95%CI: 1.78-11.87) were significantly associated with the choice of nursing as future career after the onset of the COVID-19 pandemic. Conclusions: The COVID-19 pandemic appeared to have a positive influence on the career choice of nursing among Chinese nursing students.

Comparison of Pregnancy Outcomes Between Single-Morula Embryo Transfer and Single-Blastocyst Transfer in Fresh IVF/ICSI Cycles.

BACKGROUND This study investigated the effectiveness and feasibility of day 4 (D4) morula embryo transfer (ET) in comparison with day 5 (D5) blastocyst ET, with regards to their clinical data, laboratory test results, and pregnancy outcomes. MATERIAL AND METHODS This retrospective cohort study enrolled 1070 patients, including 178 cases in group D4 and 892 cases in group D5. The endpoint was live birth rate after fresh embryo transfer. Furthermore, the clinical outcomes of D4 embryos with different morphology were compared and assigned to 3 groups: in group 1 (n=66) the embryos were compacted but not expanded, in group 2 (n=102) the embryos were compacted and expanded (early blastocyst), and in group 3 (n=10) the embryos were not compacted. RESULTS Groups D4 and D5 had comparable clinical pregnancy rates (53.37% vs. 59.97%) and live birth rates (43.25% vs 50.89%), and there were no significant differences between the 2 groups. In group 3, there was only 1 clinical pregnancy and no live birth. In comparison between group 1 and group 2, the clinical pregnancy rate of group 2 showed an upward trend (48.48% vs 60.78%), but there was no significant difference. There was also no statistically significant difference in the live birth rate between the 2 groups (42.42% vs 49.01%). CONCLUSIONS Transferring of compacted embryos or early blastocysts can result in high clinical pregnancy rates and live birth rates. In addition to the cleavage and blastocyst ET, morula ET may serve as an alternative option for the clinician.

Small molecule proteomics quantifies differences between normal and fibrotic pulmonary extracellular matrices.

BACKGROUND: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. METHODS: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 µL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 µL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. RESULTS: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin ß1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). CONCLUSIONS: Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

Blastocyst-stage versus cleavage-stage embryo transfer in the first frozen cycles of OHSS-risk patients who deferred from fresh embryo transfer.

Elective cryopreservation of all embryos has been the most effective means to avoid developing ovarian hyperstimulation syndrome (OHSS). However, it is still unknown which stage is optimal for freezing and transferring into uterus in OHSS-risk patients. This study was undertaken to evaluate whether OHSS-risk patients could benefit from transferring blastocysts. A total of 162 women were allocated to cleavage-stage embryo transfer (ET) (group A = 70) and blastocysts transfer (group B = 92) on the basis of patients' voluntary in their first frozen cycles. Although the mean number of transferred embryos in group A was significantly more than those in group B (2.37 ± 0.52 versus 2.11 ± 0.52, p < 0.05), the clinical pregnancy rates, implantation rates and live birth rates in group B were significantly higher than those in group A (47.83% versus 31.43%, p < 0.05; 31.44% versus 18.67%, p < 0.05; 40.21% versus 27.14%, p < 0.05), and the multiple pregnancy rates in both groups were comparable (34.09% versus 36.36%, p > 0.05). The observed results in OHSS-risk population allow us to take a position in favor of blastocyst transfer, thus pregnancy and live birth could be achieved with fewer ETs and in a shorter time frame.

[Extorsion traction and pushing manipulation with fingers for the treatment of anterior shoulder dislocation in elderly].

OBJECTIVE: To investigate a manipulating therapy for treatment of anterior shoulder dislocation in elderly. METHODS: From October 2011 to June 2012,27 elderly patients with anterior shoulder dislocation were treated by extorsion traction and pushing manipulation with fingers, including 7 males and 20 females aged from 65 to 86 years old with an average of 77. The course of disease ranged from 1 h to 1 d. The shoulder manifested square deformity, Dugus signs showed positive, and X-ray displayed anterior shoulder dislocation. Dugus fixation was applied for and removed external fixation at 3 weeks after operation and carried out shoulder functional exercise. Functional evaluation standard on shoulder joint injuries was used for evaluate clinical outcomes. RESULTS: All patients were gained reduction for the first time, and followed up at 3 months after operation, no dislocation occurred. According to functional evaluation standard on shoulder joint injuries, 22 cases got an excellent result,2 cases good,and 1 case moderate. CONCLUSION: Extorsion traction and pushing manipulating therapy for treatment of anterior shoulder dislocation in elderly, which has advantages of simple, convenient, less painful, and can avoid iatrogenic injury, is feasible to widespread.

Live birth following vitrification of in vitro matured oocytes derived from sibling smaller follicles at follicle selection phase in the context of in vitro fertilization.

In ovarian stimulation, a 31-year-old woman with polycystic ovary syndrome was at the risk of developing ovarian hyperstimulation syndrome, follicle aspiration was performed, and eight immature oocytes were collected from follicle fluids. After 28 h in vitro culture, six of them reached MII and were vitrified. The patient failed to conceive in her fresh in vitro fertilization cycle and next two replacement cycles. In the third replacement cycle, a successful pregnancy was obtained by vitrified-thawed oocytes. This case demonstrates that follicular aspiration during follicle selection phase has protective effects against developing ovarian hyperstimulation syndrome, and rescued immature oocytes are viable and could produce promising embryos for live birth.

Chronic hepatitis B virus infection in women is not associated with IVF/ICSI outcomes.

OBJECTIVE: This study was to evaluate whether chronic HBV (Hepatitis B virus) infection in women is associated with poor performance following IVF/ICSI (in vitro fertilization/intracytoplasmic sperm injection) treatments. MATERIALS AND METHODS: 123 cycles with female chronic HBV infection were compared with 246 cycles with no-infected couples, matched for female age, D3 serum FSH (follicles stimulation hormone) levels, body mass index and assisted reproductive technology approach used (IVF or ICSI), in a ratio of 1:2. RESULTS: The details in IVF/ICSI cycles, including the dosage of gonadotrophin used, the serum estradiol levels and the endometrial thickness on the day of hCG (human chorionic gonadotrophin) injection, the mean number of oocytes retrieved, and the embryology data, were similar among seropositive and seronegative women. And there was no significant differences in implantation rates and live birth rates between seropositive women group and matched control (30.52 versus 28.34% per transfer; 42.28 versus 40.65%). CONCLUSIONS: The results indicated that women with chronic HBV infection is not associated with outcomes of IVF/ICSI treatments.

[Suppression of mitochondrial oxidative phosphorylation on in vitro maturation, fertilization and developmental competence of oocytes].

OBJECTIVE: To investigate the roles of mitochondrial oxidative phosphorylation (OXPHOS) capacity in oocyte maturation, fertilization and embryo development. METHODS: Carbonyl cyanide p- (tri-fluromethoxy) phenyl-hydrazone (FCCP), a metabolic inhibitor of mitochondria, was introduced into culture medium. The integrity of spindle and chromosome alignment, reactive oxygen species (ROS) levels, and rates of maturation, germinal vesicle breakdown, fertilization and blastulation were assessed in vitro. RESULTS: Significant decreases were detected in the percentages of oocytes with nuclear maturation, normal spindle formation and chromosome alignment, ROS levels and capable for blastocyst formation between oocytes treated with FCCP and non-treated (control group), 55.8%, 37.9%, 0.67 and 57.9% (FCCP 10 nmol/L group), 47.3%,34.7%, 0.59 and 41.8% (FCCP 100 nmol/L group) versus 62.9%, 61.9%,0.94 and 68.3% (control group) respectively, P<0.05. However, No significant differences were found in the rates of GVBD and fertilization in oocytes from the FCCP treated and the control. CONCLUSION: Inhibition of mitochondrial metabolic capacity resulted in decreased the percentages of oocytes with nuclear maturation, normal spindle formation and chromosome alignment, ROS levels and capable for blastocyst formation. But the treatment of FCCP did not affect the rate of fertilization.

DMAP-catalyzed [3 + 2] and [4 + 2] cycloaddition reactions between [60]fullerene and unmodified Morita-Baylis-Hillman adducts in the presence of Ac2O.

One-step DMAP-catalyzed [3 + 2] and [4 + 2] cycloaddition reactions between C(60) and unmodified Morita-Baylis-Hillman adducts in the presence of Ac(2)O have been developed for the easy preparation of cyclopentene- and cyclohexene-fused [60]fullerene derivatives. When the MBH adducts bear an alkyl group, two different reaction pathways could be controlled selectively depending on the conditions.

[Effects of controlled ovarian hyperstimulation on mitochondria copy number and functions in murine oocytes].

OBJECTIVE: To investigate the effect of whether controlled ovarian hyperstimulation (COH) on mitochondrial DNA (mtDNA) copy number, mitochondrial function, distribution, the level of reactive oxygen species (ROS) in oocytes and the mechanism of oocyte loss in COH. METHODS: Matured murine oocytes were classified into COH group and natural cycles (NC) group. The copies of mtDNA, the magnitude of mitochondrial membrane potential (Δφm) and oocyte adenosine triphosphate (ATP) content, pattern of mitochondrial distribution, and ROS levels were evaluated by realtime PCR, immunofluorescence and fluorescence-luciferase mensuration. RESULTS: The copies of mtDNA, the levels of Δφm, and ATP content in oocytes between COH and NC groups showed statistical difference [(1.15 ± 0.01)×10(5), 0.34 ± 0.03 and (241 ± 20) fmol/oocyte (COH)] versus [(2.15 ± 0.19)×10(5), 0.82 ± 0.07 and (325 ± 11) fmol/oocyte (NC)], respectively(P < 0.05). However, there were no significant differences in the rate of evenly distributed mitochondria and the level of ROS in oocytes from COH and NC [(76.5% (78/102) in COH versus 82.1% (69/84)]; 1.07 ± 0.07 in COH versus 0.93 ± 0.08 in NC (P > 0.05). CONCLUSION: It was indicated that non-physiological COH treatments inhibit mtDNA replication, alter mitochondrial function, which might partly be involved in the low development potential of COH oocyte.

3,6,8-Tribromo-7-ethyl-amino-4-methyl-2H-chromen-2-one.

In the title mol-ecule, C(12)H(10)Br(3)NO(2), the 2H-chromen ring is essentially planar (r.m.s. deviation = 0.022 Å) with the ethyl-amino group oriented at 13.9 (5)° with respect to the ring. The mol-ecular structure is stabilized by intra-molecular N-H⋯Br and C-H⋯Br interactions.

3,6-Dibromo-7-ethyl-amino-4-methyl-2H-chromen-2-one.

In title compound, C(12)H(11)Br(2)NO(2), the coumarin ring system is almost planar, the two rings being inclined to one another by 1.40 (15)°. There are two short intra-molecular inter-actions (N-H⋯Br and C-H⋯Br) involving the Br atoms. In the crystal, mol-ecules stack along the a-axis direction via π-π inter-actions; the centroid-centroid distances vary from 3.6484 (19) to 3.7942 (19) Å.