Iron burden and endocrine complications in transfusion-dependent thalassemia patients In Sarawak, Malaysia: a retrospective study.

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

A Case of Persistent Junctional Reciprocating Tachycardia Coincident With Cor Triatriatum Sinister.

Persistent junctional reciprocating tachycardia is a rare form of refractory atrioventricular reentrant tachycardia that accounts for <1% of supraventricular tachycardia in pediatrics. The accessory pathways are generally isolated with few reported underlying structural heart defects. We present a case of a five-month-old male with refractory tachyarrhythmia found to have cor triatriatum sinister, which to our knowledge, is the first reported case of these two rare anomalies coexisting.

Anti-tumor activity of a novel LAIR1 antagonist in combination with anti-PD-1 to treat collagen-rich solid tumors.

We recently reported that resistance to PD-1-blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), and thus we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. Here, we report LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer. Stroma-associated myeloid cells exhibit a suppressive phenotype and correlate with LAIR1 expression in human cancer. NGM438, a novel humanized LAIR1 antagonist monoclonal antibody, elicits myeloid inflammation and allogeneic T cell responses by binding to LAIR1 and blocking collagen engagement. Further, a mouse-reactive NGM438 surrogate antibody sensitized refractory KP mouse lung tumors to anti-PD-1 therapy and resulted in increased intratumoral CD8+ T cell content and inflammatory gene expression. These data place LAIR1 at the intersection of stroma and suppressive myeloid cells and support the notion that blockade of the LAIR1/collagen axis can potentially address resistance to checkpoint inhibitor therapy in the clinic.

ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms.

Solid tumors are dense three-dimensional (3D) multicellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune-suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contribution of ILT2 and ILT4 to immune inhibition in the context of solid tumor tissue has not been fully explored. We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that although ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. In a 3D spheroid tumor model, dual ILT2/ILT4 blockade was required for the optimal activation of myeloid cells, including the secretion of CXCL9 and CCL5, upregulation of CD86 on dendritic cells, and downregulation of CD163 on macrophages. Humanized mouse tumor models showed increased immune activation and cytolytic T-cell activity with combined ILT2 and ILT4 blockade, including evidence of the generation of immune niches, which have been shown to correlate with clinical response to immune-checkpoint blockade. In a human tumor explant histoculture system, dual ILT2/ILT4 blockade increased CXCL9 secretion, downregulated CD163 expression, and increased the expression of M1 macrophage, IFNγ, and cytolytic T-cell gene signatures. Thus, we have revealed distinct contributions of ILT2 and ILT4 to myeloid cell biology and provide proof-of-concept data supporting the combined blockade of ILT2 and ILT4 to therapeutically induce optimal myeloid cell reprogramming in the tumor microenvironment.

Thyroglossal Duct Cyst Infection Caused by Neisseria gonorrhoeae: An Unusual Complication of Pharyngeal Gonorrhea.

ABSTRACT: Neisseria gonorrhoeae is a human obligate pathogen whose clinical expression of disease ranges from localized genital infection to involvement of extragenital sites such as the conjunctiva and throat. We describe the second case of a thyroglossal duct abscess due to N. gonorrhoeae, an uncommon complication of pharyngeal gonococcal infection. The fortuitous occurrence in the same individual of these 2 conditions that both exhibit an occult clinical presentation likely accounts for rarity of this infection. We discuss the pertinent gonococcal and host factors that underlie the clinical manifestations of this infection. A particular focus is the fundamental role that the binding of the gonococcal opacity-associated protein to the ubiquitous human carcinoembryonic cell adhesion molecule plays in the pathogenesis of pharyngeal gonorrhea.

Screening, brief intervention, and referral to treatment for tobacco consumption, alcohol misuse, and physical inactivity: an equity-informed rapid review.

OBJECTIVE: This rapid review systematically synthesizes evidence of the effectiveness of the Screening, Brief Intervention, and Referral (SBIR/T) approach for tobacco use, alcohol misuse, and physical inactivity. STUDY DESIGN: This was a rapid review. METHODS: We searched primary studies between 2012 and 2022 in seven electronic databases. The search strategy used concepts related to alcohol-related disorders, intoxication, cigarette, nicotine, physical activity, exercise, sedentary, screening, therapy, and referral. We reviewed both title/abstract and full-text using a priori set inclusion and exclusion criteria to identify the eligible studies. We appraised study quality, extracted data, and summarized the characteristics of the included studies. We applied health equity lenses in the synthesis. RESULTS: Of the 44 included studies, most focused on alcohol misuse. SBIR/T improved patients' attitudes toward alcohol behavior change, improved readiness and referral initiation for change, and effectively reduced alcohol consumption. Few studies pertained to smoking and physical inactivity. Most studies on smoking demonstrated effectiveness pertaining to patients' acceptance of referral recommendations, improved readiness and attempts to quitting smoking, and reduced or cessation of smoking. Findings were mixed about the effectiveness of SBIR/T in improving physical activity. Minimal studies exist on the impacts of SBIR/T for these three risk factors on healthcare resource use or costs. Studies considering diverse population characteristics in the design and effectiveness assessment of the SBIR/T intervention are lacking. CONCLUSIONS: More research on the impacts of SBIR/T on tobacco use, alcohol misuse, and physical inactivity is required to inform the planning and delivery of SBIR/T for general and disadvantaged populations.

Genetically engineered human umbilical cord-derived mesenchymal stem cells expressing human interleukin-12 and in vitro growth inhibition against lung adenocarcinoma cells.

INTRODUCTION: Mesenchymal stromal cells (MSCs) are promising vehicles for cancer therapy due to their homing ability and potency to be genetically manipulated through either viral or non-viral methods. Interleukin-12 (IL-12) is one of the key immunomodulatory cytokines which has anti-tumour effect. However, systemic administration of the cytokine at therapeutic dosage can cause serious toxicity in the host system due to the high systemic level of interferon-γ (IFN-γ) induced. OBJECTIVES: This study aimed to investigate the in vitro growth inhibition of genetically engineered human umbilical cord-derived mesenchymal stromal cells (hUCMSC) expressing IL-12 on H1975 human lung adenocarcinoma cells. MATERIALS AND METHODS: Both adenoviral method and electroporation which used to generate hUCMSC-IL12 were compared. The method with better outcome was selected to generate hUCMSC-IL12 for the co-culture experiment with H1975 or MRC-5 cells. Characterisation of hUCMSC and hUCMSC-IL12 was performed. RESULTS: Adenoviral method showed superior results in transfection efficiency (63.6%), post-transfection cell viability (82.6%) and hIL-12 protein expression (1.2 x 107 pg/ml) and thus was selected for the downstream experiments. Subsequently, hUCMSC-IL12 showed significant inhibition effect on H1975 cells after 5 days of co-culture. No significant difference was observed for all other co-culture groups, indicating that the inhibition effect was because of hIL-12. Lastly, the integrity of hUCMSC-IL12 remained unaffected by the transduction through examination of their surface markers and differentiation properties. CONCLUSION: This study provided proof of concept that hUCMSC can be genetically engineered to express hIL-12 which exerts direct growth inhibition effect on human lung adenocarcinoma cells.

Native amphibian toxin reduces invasive crayfish feeding with potential benefits to stream biodiversity.

BACKGROUND: Biodiversity is generally reduced when non-native species invade an ecosystem. Invasive crayfish, Procambarus clarkii, populate California freshwater streams, and in the Santa Monica Mountains (Los Angeles, USA), their introduction has led to trophic cascades due to omnivorous feeding behavior and a rapid rate of population growth. The native California newt, Taricha torosa, possesses a neurotoxin, tetrodotoxin (TTX), that affects freshwater animal behavior. Given P. clarkii has a limited evolutionary history with TTX, we hypothesized that TTX may affect crayfish feeding behaviors. To determine if TTX affects P. clarkii behavior, we measured cumulative movement and various feeding behaviors of P. clarkii exposed to (i) waterborne, ecologically realistic concentrations of TTX (~ 3.0 × 10- 8 moles/L), (ii) an anuran chemical cue to account for intraguild cues, or (iii) a T. torosa chemical cue with quantitated TTX in it (~ 6.2 × 10- 8 moles/L). RESULTS: We found that the presence of TTX in any form significantly reduced crayfish movement and decreased the amount of food consumed over time. Crayfish responses to the anuran treatment did not significantly differ from controls. CONCLUSION: Our laboratory results show that naturally occurring neurotoxin from native California newts limits invasive crayfish foraging and feeding rates, which may play a role in preserving local stream ecosystems by limiting invasive crayfish behaviors that are detrimental to biodiversity.

Acute leukemia and lymphoma in pregnancy, a retrospective study from a tertiary center in Malaysia.

INTRODUCTION: Most evidence about the management of cancer and hematological malignancy in pregnancy are derived from retrospective observational studies with a small sample size. Availability of sufficiently large data has enabled evidence-based decision-making in this clinical dilemma. MATERIALS AND METHODS: Retrospective study looking into patients diagnosed with acute leukemia or lymphoma in pregnancy from 1st January 2014 to 1st January 2020 in Ampang General Hospital including newly or previously diagnosed and relapsed disease RESULTS: 37 cases of acute leukemia or lymphoma in pregnancy occurred in 34 patients. Majority of acute leukemia or lymphoma in pregnancy diagnosed in 1st trimester or in the setting of previously established or relapsed disease was therapeutically terminated. Thirteen pregnancies treated with antenatal chemotherapy resulted in livebirths except one stillbirth. More adverse obstetric outcomes are observed in pregnancies that did not receive antenatal chemotherapy, but association did not reach statistical significance. There was no significant difference in fetal outcome between cohort with and without antenatal chemotherapy. No treatment related mortality was observed in pregnancies with antenatal chemotherapy. Overall survival for newly diagnosed acute leukemia in pregnancy is significantly better with antenatal chemotherapy versus no antenatal chemotherapy. CONCLUSION: Treatment with chemotherapy in 2nd trimester of pregnancy onwards appears to have tolerable risks with favorable obstetric and fetal outcome. Deferment of treatment for acute leukemia in pregnancy to after delivery may cause increased risk of maternal and fetal adverse outcome.

The effect of flushing of the common bile duct on hepatobiliary markers and short-term outcomes in dogs undergoing cholecystectomy for the management of gall bladder mucocele: A randomized controlled prospective study.

OBJECTIVE: To determine the effect of flushing of the common bile duct (CBD) on hepatobiliary markers and short-term outcome in dogs undergoing cholecystectomy for the management of gallbladder mucocele (GBM). STUDY DESIGN: Randomized, controlled, prospective study. ANIMALS: Thirty-two client-owned dogs. METHODS: Dogs were allocated randomly to either a "flush" group or a "non-flush group." Flushing was performed in a normograde fashion, followed by a routine cholecystectomy. Data collected included presenting clinical signs, preoperative and 3-day postoperative hepatobiliary markers (alkaline phosphatase, ALP; alanine aminotransferase, ALT; gamma glumatyl-transferase, GGT; bilirubin; cholesterol; triglycerides), duration of hospitalization, and complications. These data were compared between groups. RESULTS: Sixteen dogs were enrolled in each group. One dog (in the flush group) was excluded following diagnosis of hepatic lymphoma. Border terriers were overrepresented (20/31). Overall, there were marked reductions from preoperative to 3 days postoperative in serum bilirubin (p = .004), ALP (p = .020), ALT (p < .001), GGT (p = .025), and cholesterol (p < .001) values. There was no difference in any marker between groups. Survival to discharge was 90.3% (28/31 dogs). CONCLUSION: Cholestatic markers decreased significantly 3 days postcholecystectomy. No short-term clinical or clinico-pathological benefits were identified when flushing the CBD in dogs undergoing cholecystectomy for GBM. CLINICAL SIGNIFICANCE: The findings of the study do not support routine flushing of the CBD during cholecystectomy for GBM in dogs.

Underreporting and Underrepresentation of Racial and Ethnic Minority Patients in Lymphedema Clinical Trials: A Systematic Review.

The generalizability of findings from Clinical Trials (CTs) investigating lymphedema treatment modalities requires an accurate representation of the target population. This study aims to evaluate racial and ethnic reporting and representation in lymphedema CTs. A comprehensive systematic literature search was conducted during May 2023 using multiple databases, following the PRISMA guidelines. All CTs published from 2018 to 2023 were included. A total of 84 articles were included in this review, from which 6,546 participants were included in the analysis. Seventy-four (88.1%) articles addressed secondary lymphedema, of which 60 (81.1%) were related to breast cancer. Only 12 (13%) of CTs reported at some extend race or ethnicity. Of these, five (41.6%) reported race and two (16.6%) reported ethnicity according to FDA guidelines. White race had the highest pooled prevalence (80%; 95% CI 72-86%; I2=90%), followed by Black (7%; 95% CI 2- 15%; I2= 94.3%) and Asian (4%; 95% CI 1-8%; I2= 89.9%). In studies reporting ethnicity, participants were predominantly non-Hispanic (92.1%; 95% CI 90 - 94%). There is an underreporting and underrepresentation of racial and ethnic minorities among lymphedema CTs, limiting their generalizability. It is imperative to future development of strategies to enhance diversity in the study sample.

A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization.

Decidualization is the hormone-dependent process of endometrial remodeling that is essential for fertility and reproductive health. It is characterized by dynamic changes in the endometrial stromal compartment including differentiation of fibroblasts, immune cell trafficking and vascular remodeling. Deficits in decidualization are implicated in disorders of pregnancy such as implantation failure, intra-uterine growth restriction, and pre-eclampsia. Androgens are key regulators of decidualization that promote optimal differentiation of stromal fibroblasts and activation of downstream signaling pathways required for endometrial remodeling. We have shown that androgen biosynthesis, via 5α-reductase-dependent production of dihydrotestosterone, is required for optimal decidualization of human stromal fibroblasts in vitro, but whether this is required for decidualization in vivo has not been tested. In the current study we used steroid 5α-reductase type 1 (SRD5A1) deficient mice (Srd5a1-/- mice) and a validated model of induced decidualization to investigate the role of SRD5A1 and intracrine androgen signaling in endometrial decidualization. We measured decidualization response (weight/proportion), transcriptomic changes, and morphological and functional parameters of vascular development. These investigations revealed a striking effect of 5α-reductase deficiency on the decidualization response. Furthermore, vessel permeability and transcriptional regulation of angiogenesis signaling pathways, particularly those that involved vascular endothelial growth factor (VEGF), were disrupted in the absence of 5α-reductase. In Srd5a1-/- mice, injection of dihydrotestosterone co-incident with decidualization restored decidualization responses, vessel permeability, and expression of angiogenesis genes to wild type levels. Androgen availability declines with age which may contribute to age-related risk of pregnancy disorders. These findings show that intracrine androgen signaling is required for optimal decidualization in vivo and confirm a major role for androgens in the development of the vasculature during decidualization through regulation of the VEGF pathway. These findings highlight new opportunities for improving age-related deficits in fertility and pregnancy health by targeting androgen-dependent signaling in the endometrium.

Bortezomib-induced neurotoxicity in human neurons is the consequence of nicotinamide adenine dinucleotide depletion.

The proteosome inhibitor bortezomib has revolutionized the treatment of multiple hematologic malignancies, but in many cases, its efficacy is limited by a dose-dependent peripheral neuropathy. We show that human induced pluripotent stem cell (hiPSC)-derived motor neurons and sensory neurons provide a model system for the study of bortezomib-induced peripheral neuropathy, with promising implications for furthering the mechanistic understanding of and developing treatments for preventing axonal damage. Human neurons in tissue culture displayed distal-to-proximal neurite degeneration when exposed to bortezomib. This process coincided with disruptions in mitochondrial function and energy homeostasis, similar to those described in rodent models of bortezomib-induced neuropathy. Moreover, although the degenerative process was unaffected by inhibition of caspases, it was completely blocked by exogenous nicotinamide adenine dinucleotide (NAD+), a mediator of the SARM1-dependent axon degeneration pathway. We demonstrate that bortezomib-induced neurotoxicity in relevant human neurons proceeds through mitochondrial dysfunction and NAD+ depletion-mediated axon degeneration, raising the possibility that targeting these changes might provide effective therapeutics for the prevention of bortezomib-induced neuropathy and that modeling chemotherapy-induced neuropathy in human neurons has utility.

Validation of the Anti-Inflammatory Effect of Tenebrio Molitor Larva Oil in a Colitis Mouse Model.

Ulcerative colitis is caused by various external factors and is an inflammatory disease that causes decreased intestinal function. Tenebrio molitor larvae contain more than 30 % fat, and the fat component consists of 45 % oleic acid, 20 % linoleic acid and 20 % polyunsaturated fatty acids. In this study, after administering Tenebrio molitor larva oil (TMLO) in a dextran sodium sulphate (DSS)-induced ulcerative colitis mouse model, the pathological findings and inflammatory markers of colitis were analysed to assess whether a colitis mitigation effect was achieved. In the TMLO-administered group, the colon length increased, the spleen weight decreased, and the body weight increased compared with that in the DSS group. In addition, the disease activity index level decreased, the mRNA expression level of inflammatory cytokines in the colon decreased, and the myeloperoxidase activity level significantly decreased. Also, the activity of the NF-κB pathway involved in the regulation of the inflammatory response was lower in the TMLO group than in the DSS group. Taken together, these results suggest that TMLO suppresses occurrence of acute ulcerative colitis in the DSS mouse model. Therefore, TMLO has the potential to be developed as a health food for the prevention and treatment of ulcerative colitis.

Sperm-specific proteins: new implications for diagnostic development and cancer immunotherapy.

Spermatozoa are comprised of many unique proteins not expressed elsewhere. Sperm-specific proteins are first expressed at puberty, after the development of immune tolerance to self-antigens, and have been assumed to remain confined inside the seminiferous tubules, protected from immune cell recognition by various mechanisms of testicular immune privilege. However, new data has shown that sperm-specific proteins are released by the tubules into the surrounding interstitial fluid; from here they can contact immune cells, potentially promote immune tolerance, and enter the circulation. These new findings have clinical implications for diagnostics and therapeutics targeted at a specific class of proteins known as cancer-testis antigens (CTA), the opportunity to identify new communication pathways in the testis, and to discover new ways to monitor testis function.

Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer.

BACKGROUND: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. METHODS: Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours. RESULTS: We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. CONCLUSION: Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.

Avoiding data loss: Synthetic MRIs generated from diffusion imaging can replace corrupted structural acquisitions for freesurfer-seeded tractography.

Magnetic Resonance Imaging (MRI) motion artefacts frequently complicate structural and diffusion MRI analyses. While diffusion imaging is easily 'scrubbed' of motion affected volumes, the same is not true for T1w or T2w 'structural' images. Structural images are critical to most diffusion-imaging pipelines thus their corruption can lead to disproportionate data loss. To enable diffusion-image processing when structural images are missing or have been corrupted, we propose a means by which synthetic structural images can be generated from diffusion MRI. This technique combines multi-tissue constrained spherical deconvolution, which is central to many existing diffusion analyses, with the Bloch equations that allow simulation of MRI intensities for given scanner parameters and magnetic resonance (MR) tissue properties. We applied this technique to 32 scans, including those acquired on different scanners, with different protocols and with pathology present. The resulting synthetic T1w and T2w images were visually convincing and exhibited similar tissue contrast to acquired structural images. These were also of sufficient quality to drive a Freesurfer-based tractographic analysis. In this analysis, probabilistic tractography connecting the thalamus to the primary sensorimotor cortex was delineated with Freesurfer, using either real or synthetic structural images. Tractography for real and synthetic conditions was largely identical in terms of both voxels encountered (Dice 0.88-0.95) and mean fractional anisotropy (intrasubject absolute difference 0.00-0.02). We provide executables for the proposed technique in the hope that these may aid the community in analysing datasets where structural image corruption is common, such as studies of children or cognitively impaired persons.

Leukemia inhibitory factor-receptor signalling negatively regulates gonadotrophin-stimulated testosterone production in mouse Leydig Cells.

Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is influenced by various paracrine factors. The leukemia inhibitory factor receptor (LIFR) is expressed in the testis and activated by different ligands, including leukemia inhibitory factor (LIF), produced by peritubular myoid cells. LIF can modulate LC testosterone production in vitro under certain circumstances, but the role of consolidated signalling through LIFR in adult LC function in vivo has not been established. We used a conditional Lifr allele in combination with adenoviral vectors expressing Cre-recombinase to generate an acute model of LC Lifr-KO in the adult mouse testis, and showed that LC Lifr is not required for short term LC survival or basal steroidogenesis. However, LIFR-signalling negatively regulates steroidogenic enzyme expression and maximal gonadotrophin-stimulated testosterone biosynthesis, expanding our understanding of the intricate regulation of LC steroidogenic function.