Treatment modalities for granulomatous mastitis, seeking the most appropriate treatment with the least recurrence rate: a systematic review and meta-analysis.

BACKGROUND: Granulomatous mastitis (GM) is a rare, benign, inflammatory breast disease with an unknown etiology that predominantly affects women of reproductive age. The definitive treatment of GM is currently controversial; an appropriate therapeutic strategy has yet to be identified, and the disease's high recurrence rate remains. This study aims to determine the recurrence rate for each GM treatment strategy to identify the most appropriate treatment modality. METHODS: The search for relevant articles was undertaken using three international databases, including Medline, Scopus, and Web of Science. Articles published in English until the end of 2021 evaluating the recurrence rate of GM were included. Using Stata 13.0, the pooled incidence and 95% confidence interval (CI) for the recurrence rate were determined. RESULTS: Sixty-five eligible studies were included in our study. The recurrence rates of systemic steroid use, topical steroid use, antibiotic use, methotrexate use, observation, drainage, excision, antibiotic use and surgery, steroid use and surgery, antibiotic and steroid use, methotrexate and steroid use were 24% (95% CI: 21-27%), 11% (95% CI: 6-21%), 18% (95% CI: 14-22%), 13% (95% CI: 7-22%), 11% (95% CI: 7-17%), 65% (95% CI: 50-78%), 13% (95% CI: 10-16%), 23% (95% CI: 14-36%), 7% (95% CI: 5-11%), 11% (95% CI: 6-18%), and 4% (95% CI: 2-8%), respectively. Drainage had the highest recurrence rate, while combined methotrexate and steroid treatment had the lowest rate. CONCLUSION: The optimal treatment strategy for GM depends on the disease's severity, consequences, and the patient's features. The study results indicate that combination therapy is preferable for minimizing the risk of relapse and reducing treatment complications.

Omega-3 Adjunctive Therapy in Idiopathic SSNHL: A Randomised, Triple-Blind, Placebo-Controlled Trial.

Introduction: Idiopathic Sudden Sensorineural Hearing Loss as a subset of sensorineural hearing loss will be confirmed by a progressive hearing loss of at least 30 dB at three contiguous frequencies over 72 hours or less. A sudden or abrupt hearing loss correlates with the time course, and a vascular event is presumptive aetiology. There is an inverse association between Omega-3 consumption and hearing loss. This study aimed to evaluate the efficacy of Omega-3 adjunctive therapy in Idiopathic Sudden Sensorineural Hearing Loss by audiometric assessments. Materials and Methods: In this randomised, triple-blind, placebo-controlled trial, all participants aged 18-70 with a history of sudden deafness (within 12 hours and ≤ 30 days) were eligible for enrollment. They were included if audiology diagnostic tests confirmed the SSNHL. Ultimately, they were randomised to the Omega-3 group and the placebo group. Results: Thirty-three patients were randomly allocated to the Omega-3 group and thirty-two to the placebo group. Vertigo (32.3% of all patients) and underlying conditions had significant relationships with complete response (C.R.)-final hearing level ≤of 25 dB in pure-tone average (P < 0.05). There was no significant difference between both groups before and after treatment. Although it was not statistically significant, patients in the Omega-3 group had faster recovery than placebo. Conclusions: Omega-3 adjunctive therapy did not have a therapeutic effect on SSNHL patients. Moreover, C.R. happened in half the patients. Vertigo and underlying conditions considerably worsen the recovery from SSNHL.

The role of fetal heart rate in first trimester sonograms in prediction of fetal sex: a systematic review and meta-analysis.

BACKGROUND: Early fetal sex determination is worthy of providing alertness about possible x-linked disorders, as well as predicting sex-related pregnancy complications and outcomes. Satisfying the curiosity of parents is another advantage. In this way, several studies have been performed which have shown conflicting results. AIM: We planned a systematic review for identifying any plausible role of Fetal Heart Rate (FHR) for early predicting fetal sex during the first trimester of non-complicated pregnancies. METHODS: This is a meta-analysis in which PubMed and Scopus databases were searched using different related keywords to find similar articles up to December 2022. Then the articles were screened to find eligible articles and finally, the articles entered in the meta-analysis were analyzed using Stata software (Stata Corp, College Station, TX). Standardized mean difference (SMD) and their 95% confidence interval (CI) were estimated. RESULTS: A total of 223 articles were evaluated and five articles were included in the meta-analysis. The results showed that there is a significant heterogeneity between the articles (p = 0.012, I-squared = 69.0%). The results of meta-analysis with a random model showed that there is no significant difference between male and female genders in terms of mean FHR (SMD = 0.04, 95%CI = -0.09-0.16, Z = 0.59, p = 0.553). CONCLUSION: This systematic review and meta-analysis showed that even though male fetuses show faster FHR but such sex-related difference is minimal. Therefore, first-trimester FHR is not a reliable predictive test for fetal sex determination. Further studies are recommended to achieve a more precise conclusion. TRIAL REGISTRATION: PROSPERO: CRD42023418291.

In vitro clonal multilineage differentiation of distinct murine hematopoietic progenitor populations.

Here we describe an in vitro co-culture system that can differentiate hematopoietic progenitor populations to all major hematopoietic lineages at clonal level. We present both a sensitive single-cell switch-culture system as well as a less laborious alternative barcoding protocol more convenient for larger cell numbers. Importantly, generation of all lineages from single long-term hematopoietic stem cells are described, following 21 days of culture. This protocol represents an efficient tool for validation experiments for single-cell genomics data. For complete details on the use and execution of this protocol, please refer to Safi et al. (2022).1.

Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction.

The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 571 transcription factor motifs reveals a population of LSK FMS-like tyrosine kinase 3 (Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures, pointing to a simultaneous gain of both lympho-myeloid and megakaryocyte-erythroid programs. Molecularly and functionally, these cells position between stem cells and committed progenitors and display multi-lineage capacity in vitro and in vivo but lack self-renewal activity. This integrative molecular analysis resolves the heterogeneity of cells along hematopoietic differentiation and permits investigation of chromatin-mediated transition between multipotency and lineage restriction.

The Effect of Total Knee Arthroplasty on Hindfoot Alignment in Patients with Severe Genu Varum and Genu Valgum.

BACKGROUND: The maintenance of deformity in the ankle and hindfoot after correction of knee deformity following knee arthroplasty may cause abnormal tension in the knee and patient dissatisfaction. The aim of this study was to determine the effect of knee arthroplasty on the hindfoot alignment in patients with severe genu varum and valgum. METHODS: A total of 84 patients with primary osteoarthritis, were enrolled in the study. The knee deformity was measured using a long leg film before surgery. The long axial radiographic view of hindfoot was taken in the standing position for all patients, before and six months after surgery. Comparisons were made on changes in the hindfoot angles measured before and after surgery. RESULTS: A total of 84 patients with mean age of 62.28 ± 7.77 years, 77 (92%) and seven patients (eight percent) had knee varus and valgus deformity, respectively. In the knee varus group, the mean preoperative hindfoot angle was + 5.32 ± 6.12 ° (valgus) which was changed to - 0.25 ± 4.91 ° (varus) in the postoperative phase. In the knee valgus group, the mean pre and postoperative hindfoot angles were - 7.71 ± 7.06° (varus) and - 2.14 ± 5.92 ° (varus), respectively. The mean preoperative hindfoot angle in severe and very severe varus knee groups were + 5.45 ± 3.30 and + 5.28 ± 6.86 °, respectively. These angles were changed to + 0.21± 5.17 and -1.60 ± 3.89° six months after surgery, respectively. The mean preoperative hindfoot angle in severe and very severe valgus knee deformity groups were - 7.00 ± 4.69 and -8.66 ± 10.69 °, respectively. These angles were changed to - 2.00 ± 5.71 and - 2.33 ± 7.50 °after surgery, respectively. There was no significant difference between patients with severe and very severe deformity in terms of pre and post-operative hindfoot angle. CONCLUSION: The hindfoot alignment is significantly corrected after knee arthroplasty. The severity of knee deformity does not correlate with the severity of the hindfoot deformity before and after surgery.

Correction: S100A6 is a critical regulator of hematopoietic stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

S100A6 is a critical regulator of hematopoietic stem cells.

The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell numbers in the HSC compartment, decreased myeloid output, and increased apoptotic HSC numbers in steady state. S100A6KO HSCs had impaired self-renewal and regenerative capacity, not responding to 5-Fluorouracil. Our transcriptomic and proteomic profiling suggested that S100A6 is a critical HSC regulator. Intriguingly, S100A6KO HSCs showed decreased levels of phosphorylated Akt (p-Akt) and Hsp90, with an impairment of mitochondrial respiratory capacity and a reduction of mitochondrial calcium levels. We showed that S100A6 regulates intracellular and mitochondria calcium buffering of HSC upon cytokine stimulation and have demonstrated that Akt activator SC79 reverts the levels of intracellular and mitochondrial calcium in HSC. Hematopoietic colony-forming activity and the Hsp90 activity of S100A6KO are restored through activation of the Akt pathway. We show that p-Akt is the prime downstream mechanism of S100A6 in the regulation of HSC self-renewal by specifically governing mitochondrial metabolic function and Hsp90 protein quality.

An investigation into the effect of evening primrose in dilatation of cervix and pain during and after hysterosalpingography.

Hysterosalpingography is one of the essential diagnostic methods for examining women who have difficulty becoming pregnant. This procedure is somehow invasive and is associated with numerous complications such as allergic sensitivity, pain, abdominal cramps and shock. Therefore, this study aimed to investigate the effect of evening primrose on cervical length and pain during and after hysterosalpingography. In this double-blind clinical trial, 66 candidates for hysterosalpingography were randomly divided into two groups. A group received 1000 mg of evening primrose orally for two days prior to hysterosalpingography, while the control group received a placebo drug similar in size to evening primrose three days prior to hysterosalpingography. The pain level was recorded based on the Visual Analogue Scale (VAS), during tenaculum placement but also immediately and four hours after hysterosalpingography. Finally, the data were analyzed using SPSS (version 20). There was a significant difference between the two groups in terms of pain during insertion of speculum and injection of the contrast medium (p <0.05). Less pain was reported in the evening primrose group compared to placebo. There was no significant difference between the two groups in terms of the length and diameter of the cervix (p <0.05). Given the fact that it is a medicinal plant with no complications and can reduce pain during speculum insertion and during contrast medium injection, evening primrose seems to be a good drug for managing pain during hysterosalpingography.

First trimester determination of fetal gender by ultrasonographic measurement of anogenital distance: A cross-sectional study.

BACKGROUND: In some patients with a family history of the gender-linked disease, determination of the fetal gender in the first trimester of pregnancy is of importance. In X-linked recessive inherited diseases, only the male embryos are involved, while in some conditions, such as congenital adrenal hyperplasia, female embryos are affected; hence early determination of fetal gender is important. OBJECTIVE: The aim of the current study was to predict the gender of the fetus based on the accurate measurement of the fetal anogenital distance (AGD) by ultrasound in the first trimester. MATERIALS AND METHODS: To determine the AGD and crown-rump length in this cross-sectional study, 316 women with singleton pregnancies were exposed to ultrasonography. The results were then compared with definitive gender of the embryos after birth. RESULTS: The best cut-off for 11 wk to 11 wk, 6 days of pregnancy was 4.5 mm, for 12 wk to 12 wk, 6 days was 4.9 mm, and for 13 wk to 13 wk, 6 days was 4.8 mm. CONCLUSION: AGD is helpful as an ultrasonographic marker that can determine fetal gender in the first trimester, especially after 12 wks.

Comparison of midazolam and dexmedetomidine for pain relief during and after hysterosalpingography in women with infertility.

Patients feel uncomfortable with cervical manipulation, uterine distension and stimulation of peritoneum during hysterosalpingography (HSG) and experience lower abdominal pain during and after the procedure. Pain during the procedure has a negative effect on the adaptation of patients to treatment and physicians are trying to overcome this unpleasant situation. Therefore, the aim of this study was to compare the effect of midazolam and dexmedetomidine on reducing pain and spasm of fallopian tubes during and after HSG procedure in women with infertility. In a double-blind randomized controlled trial, 102 patients were randomly divided into two groups, midazolam and dexmedetomidine. The pain was recorded during injection and immediately after injection and 30 minutes after HSG, and then the complications of injection were recorded. Finally, the data were analyzed using SPSS version 20. Based on the results presented herein, no significant difference was found between the two groups in terms of vasovagal reaction, spasticity of the tube and the side of the spastic tube and uterine cavity anomalies (p <0.05). However, the pain showed a significant difference between the two groups during the injection, immediately or at 30 minutes after the procedure (p = 0.0001). The pain in the midazolam group was less than that of dexmedetomidine. Furthermore, there was no significant difference between the two groups regarding spasticity (p <0.05). There is a benefit in terms of pain reduction with the use of dexmedetomidine when comparing with midazolam injection. However, dexmedetomidine does not cause side effects in patients and can be used to reduce pain during injection.

Effect of intramuscular hyoscine-n-butyl bromide on fallopian tube spasm and pain perception during and after hysterosalpingography in infertile women: A randomized single-blind controlled clinical trial.

Background: Hysterosalpingography plays an important role in diagnostic work-up and treatment planning for infertile women. This procedure is usually uncomfortable and painful. The present study plans to investigate the effect of intramuscular Hyoscine-N-Butyl Bromide (HBB) on fallopian tube spasm and pain perception during and after hysterosalpingography (HSG) in infertile women. Methods: This randomized single-blind controlled clinical trial (IRCT2017021132455N2) was conducted on infertile women scheduled for HSG in one radiology clinic affiliated to Arak University of Medical Sciences between July and August 2017. Patients were selected by convenience sampling and were randomly assigned to HBB (n=50) and a control group (n=50). Women received 20 mg/1cc HBB intramuscularly in the intervention group, 30 minutes before the procedure. Women in the control group did not receive any medication. The patients were requested to complete the Numeric Pain Rating Scale after injection of the dye, and also 30 minutes following the end of the HSG. Presence or absence of tubal spasm was determined after checking the radiographic images. For the data analysis using SPSS version 18, descriptive statistics, and analytical tests such as independent sample t-test, Mann- Whitney test, chi-square or Fisher's exact tests and logistic regression and ANCOVA were used. Results: Statistically significant differences were not observed in pain scores between the HBB and the control groups at the point of dye injection and 30 minutes after ending the HSG (p>0.05). Also, tubal spasm in the HBB group was lower than in the control group, but the differences were not statistically significant between the two groups (p=0.37). Conclusion: The use of intramuscular HBB before HSG has no advantage in reducing tubal spasm and the induced pain during dye injection and 30 minutes after the HSG procedure. Thus, we don't recommend HBB use before the HSG in order to relief from pain and spasm.

Relationship between Femoral Intercondylar Notch Narrowing in Radiography and Anatomical and Histopathologic Integrity of Anterior Cruciate Ligament in Patients Undergoing Total Knee Replacement Surgery.

BACKGROUND: The presence of cruciate ligaments is very important for normal knee kinematics. Knee arthroplasty prostheses, in which these ligaments are maintained, have better kinematics. The aim of the present study was to investigate the association between femoral intercondylar notch (FIN) narrowing in radiography and clinical and histopathologic integrity of anterior cruciate ligament (ACL) in patients undergoing knee replacement surgery. METHODS: FIN index was measured in tunnel view radiography of the knees of 102 candidates of knee replacement surgery. The anatomical status of ACL was also examined during total knee arthroplasty (TKA). ACL was removed and sent for histopathologic examination to assess its degeneration rate. The association between the FIN index and the clinical and histopathological health of ACL was investigated. RESULTS: Among 102 patients with mean age of 69.73 ± 7.81 years , 39 patients (38.32%) had no or torn ACL, 31 patients (30.39%) had weak ACL, and 32 (31.37%) had normal ACL. There was a significant association between age and clinical status of ACL during surgery (P=0.017). There was a significant difference in FIN and ACL health status during surgery between the two groups with an index of more and less than 0.252 (P=0.019 and P=0.019, respectively). There was no significant difference in the mean total degeneration score (TDS) of ACL between the two groups with FIN more and less than 0.252 (P=0.816). CONCLUSION: There was a significant difference between the age and FIN narrowing (less than 0.252) as well as ACL clinical status during surgery. FIN narrowing had no significant effect on the severity of ACL degeneration and there was no significant difference in the severity of degenerative histopathologic changes between healthy and attenuated ACLs. This indicates that if ACL exists, although apparently attenuated, it has the histologic characteristic of a healthy ligament.

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations.

Immunophenotypic characterization and molecular analysis have long been used to delineate heterogeneity and define distinct cell populations. FACS is inherently a single-cell assay, however prior to molecular analysis, the target cells are often prospectively isolated in bulk, thereby losing single-cell resolution. Single-cell gene expression analysis provides a means to understand molecular differences between individual cells in heterogeneous cell populations. In bulk cell analysis an overrepresentation of a distinct cell type results in biases and occlusions of signals from rare cells with biological importance. By utilizing FACS index sorting coupled to single-cell gene expression analysis, populations can be investigated without the loss of single-cell resolution while cells with intermediate cell surface marker expression are also captured, enabling evaluation of the relevance of continuous surface marker expression. Here, we describe an approach that combines single-cell reverse transcription quantitative PCR (RT-qPCR) and FACS index sorting to simultaneously characterize the molecular and immunophenotypic heterogeneity within cell populations. In contrast to single-cell RNA sequencing methods, the use of qPCR with specific target amplification allows for robust measurements of low-abundance transcripts with fewer dropouts, while it is not confounded by issues related to cell-to-cell variations in read depth. Moreover, by directly index-sorting single-cells into lysis buffer this method, allows for cDNA synthesis and specific target pre-amplification to be performed in one step as well as for correlation of subsequently derived molecular signatures with cell surface marker expression. The described approach has been developed to investigate hematopoietic single-cells, but have also been used successfully on other cell types. In conclusion, the approach described herein allows for sensitive measurement of mRNA expression for a panel of pre-selected genes with the possibility to develop protocols for subsequent prospective isolation of molecularly distinct subpopulations.

Congenital urogenital abnormalities in children with congenital hypothyroidism.

Background: Congenital hypothyroidism (CH), as one of the most common congenital endocrine disorders, may be significantly associated with congenital malformations. This study investigates urogenital abnormalities in children with primary CH (PCH). Methods: This case-control study was conducted on 200 children aged three months to 1 year, referred to Amir-Kabir Hospital, Arak, Iran. One hundred children with PCH, as the case group, and 100 healthy children, as the control group, were selected using convenient sampling. For all children, demographic data checklists were filled, and physical examination, abdomen and pelvic ultrasound and other diagnostic measures (if necessary) were performed to evaluate the congenital urogenital abnormalities including anomalies of the penis and urethra, and disorders and anomalies of the scrotal contents. Results: Among 92 (100%) urogenital anomalies diagnosed, highest frequencies with 37 (40.2%), 26(28.2%) and 9 (9.7%) cases including hypospadias, Cryptorchidism, and hydrocele, respectively. The frequency of urogenital abnormalities among 32 children with PCH, with 52 cases (56.5%) was significantly higher than the frequency of abnormalities among the 21 children in the control group, with 40 cases (43.4%). (OR=2.04; 95%CI: 1.1-3.6; p=0.014). Conclusion: Our study demonstrated that PCH is significantly associated with the congenital urogenital abnormalities. However, due to the lack of evidence in this area, further studies are recommended to determine the necessity of conducting screening programs for abnormalities of the urogenital system in children with CH at birth.

Congenital anomalies of kidney and upper urinary tract in children with congenital hypothyroidism; a case-control study.

INTRODUCTION: Congenital hypothyroidism (CH) may be significantly associated with congenital malformations. However, there is little evidence on the relationship between renal and urinary tract anomalies and CH. OBJECTIVES: The aim of this study was to compare the renal and upper urinary tract anomalies in children with and without primary CH (PCH). PATIENTS AND METHODS: This case-control study was conducted on 200 children aged 3 months to 1 year, referring to Amir-Kabir hospital, Arak, Iran. One hundred children with PCH, as the case group, and 100 children without CH, as the control group, were selected. For all children, ultrasonography and other diagnostic measures (if necessary) were performed to evaluate renal and upper urinary tract anomalies (ureter and bladder). RESULTS: The frequency of renal and upper urinary tract anomalies among 43 children with primary CH, with 83 cases (72.8%), was significantly higher than the frequency of anomalies among the 19 children in the control group, with 31 cases (27.1%) (OR = 3; CI 95%: 1.6-5.4; P = 0.001). Among the anomalies studied, only the differences in frequency of uretero-pelvic junction obstruction (UPJO) (OR = 6; CI 95%: 1.3-28; P = 0.018) and hydronephrosis (OR = 22; CI 95%: 5-95; P = 0.001) was significant between the two groups. CONCLUSION: Our study demonstrated that PCH is significantly associated with the frequency of congenital anomalies of the kidneys and upper urinary tracts. However, further studies are recommended to determine the necessity of conducting screening programs for anomalies of the kidneys and urinary tract in children with CH at birth.

Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Nephrolithiasis in children is associated with a high rate of complications and recurrence. OBJECTIVES: Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. RESULTS: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group. CONCLUSIONS: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field.

Optogenetic control of insulin secretion in intact pancreatic islets with ß-cell-specific expression of Channelrhodopsin-2.

Insulin is secreted from the pancreatic ß-cells in response to elevated glucose. In intact islets the capacity for insulin release is determined by a complex interplay between different cell types. This has made it difficult to specifically assess the role of ß-cell defects to the insulin secretory impairment in type 2 diabetes. Here we describe a new approach, based on optogenetics, that enables specific investigation of ß-cells in intact islets. We used transgenic mice expressing the light-sensitive cation channel Channelrhodopsin-2 (ChR2) under control of the insulin promoter. Glucose tolerance in vivo was assessed using intraperitoneal glucose tolerance tests, and glucose-induced insulin release was measured from static batch incubations. ChR2 localization was determined by fluorescence confocal microscopy. The effect of ChR2 stimulation with blue LED light was assessed using Ca(2+) imaging and static islet incubations. Light stimulation of islets from transgenic ChR2 mice triggered prompt increases in intracellular Ca(2+). Moreover, light stimulation enhanced insulin secretion in batch-incubated islets at low and intermediate but not at high glucose concentrations. Glucagon release was not affected. Beta-cells from mice rendered diabetic on a high-fat diet exhibited a 3.5-fold increase in light-induced Ca(2+) influx compared with mice on a control diet. Furthermore, light enhanced insulin release also at high glucose in these mice, suggesting that high-fat feeding leads to a compensatory potentiation of the Ca(2+) response in ß-cells. The results demonstrate the usefulness and versatility of optogenetics for studying mechanisms of perturbed hormone secretion in diabetes with high time-resolution and cell-specificity.