Evaluation of Radiological and Functional Outcome of Intra-articular Proximal Tibia Plateau Fracture Treated with Plating.

Introduction: Proximal tibial plateau fractures are one of the major problems in orthopaedic surgery and are associated with high complication rates. Intra-articular proximal tibia plateau fractures represent approximately 1% of fractures in adults. Various modalities of proximal tibial plateau fracture management have been considered, ranging from simple external fixators in impending compartment syndrome to periarticular proximal tibia plates and inter-locking nails with poller screws. Purpose of this study is to determine clinical outcomes of proximal tibial plateau fractures treated with plate. Materials and methods: We did this study of proximal tibial plateau fracture according to Schatzker's classification treated with proximal tibial periarticular plates in 53 patients prospectively admitted at the author's institute from June 2018 to May 2020 with follow-up period of 6 months. Results: In our study, the average knee score was 89.30 (ranging from 79 to 93) and functional knee score was 97.92 (ranging from 75 to 100). Fifty-one (51) patients (96.23%) showed excellent results and 2 patients (3.77%) showed good results according to Knee Society Score, which suggest that internal fixation of proximal tibia plateau fracture with plating provides better results. Out of 53 patients, 9 patients had post-operative complications. Average radiological union was seen at 14 weeks. Conclusion: Locking compression plate in proximal tibia plateau fractures act as a good biological fixation provide stable fixation, articular reduction and limb alignment even in difficult fracture situations. Fixation of proximal tibia plateau fractures with plate gives excellent to good knee society score, with satisfactory functional and radiological outcome.

Evaluation of Results of Open Reduction and Internal Fixation (ORIF) of Fracture of Distal End of Femur with Intra-Articular Extension.

INTRODUCTION: Fractures of the distal femur account for 0.4% of all fractures. They involve about 7% of all femur fractures, with bimodal age distribution, commonly occur during high-velocity trauma of motor vehicle accidents in the younger group of patients and are frequently associated with other skeletal injuries. The treatment of distal femoral fractures has evolved from conservative treatment to more aggressive operative treatment. The aim is to achieve and maintain a good reduction of the joint to allow early active mobilisation, thus minimising the joint stiffness and severe muscular atrophy encountered in the conservative treatment. MATERIALS AND METHODS: This is a retrospective study of 25 patients with distal femur fracture with intra-articular extension treated with open reduction and internal fixation with DFLP, admitted at our institute between 2016 to 2019, with a minimum follow-up of six months. RESULTS: In our study, 19 (76%) patients had excellent to good results. Three (12%) patients had fair outcomes, and three (12%) patients had poor outcomes according to Neer's score. The average time for bone union in closed fractures was earlier (4.25 months) than open fractures, averaging 5.86 months. The outcome was almost similar between closed and open fractures. There were 2 (8%) cases of infection in the early post-operative period, 7 (12%) patients suffered from knee stiffness, and there were 3 (12%) cases with a pre-operative bone loss that required bone grafting. CONCLUSION: Management of complex intra-articular distal femur fracture has always been a challenge. Anatomical reduction of articular fragments and rigid fixation of these fractures are a must. DFLP provides angular stability with multiple options to secure fixation of both metaphyseal and articular fragments with the restoration of the joint congruity, limb length, alignment and rotation, allowing early mobilisation and aggressive physiotherapy without loss of fixation, resulting in gratifying functional outcome and low complication rate.

Expression map of entry receptors and infectivity factors for pan-coronaviruses in preimplantation and implantation stage human embryos.

PURPOSE: To predict if developing human embryos are permissive to multiple coronaviruses. METHOD: We analyzed publicly available single-cell RNA-seq datasets of human embryos for the known canonical and non-canonical receptors and spike protein cleavage enzymes for multiple coronaviruses like SARS-CoV, SARS-CoV-2, MERS-CoV, hCoV-229E, and hCoV-NL63. We also analyzed the expression of host genes involved in viral replication, host proteins involved in viral endosomal sorting complexes required for transport (ESCRT), genes of host proteins that physically interact with proteins of SARS-CoV-2, and the host genes essential for coronavirus infectivity. RESULTS: Of the known receptors of SARS viruses, ACE2, BSG, GOLGA7, and ZDHHC5 were expressed in different proportions in the zygote, 4-cell, 8-cell, morula, and blastocysts including the trophectoderm. The MERS-CoV receptor, DPP4, and hCoV-229E receptor, ANPEP, were expressed mainly from the compact morula to the blastocyst stages. Transcripts of the MERS-CoV alternate receptor LGALS1 were detected in most cells at all stages of development. TMPRSS2 transcripts were detected in the epiblast, primitive endoderm, and trophectoderm, while transcripts of the endosomal proteases CTSL, CTSB, and FURIN were expressed in most cells at all stages of development. ACE2 and TMPRSS2 were co-expressed in a proportion of epiblast and trophectoderm cells. The embryonic cells expressed genes involved in ESCRT, viral replication, SARS-CoV-2 interactions, and coronavirus infectivity. The ACE2 and TMPRSS2 co-expressing cells were enriched in genes associated with lipid metabolism, lysosome, peroxisome, and oxidative phosphorylation pathways. CONCLUSION: Preimplantation and implantation stage human embryos could be permissive to multiple hCoVs.

Cutaneous paraneoplastic syndrome associated with anal squamous cell carcinoma: a rare presentation of an uncommon cancer.

Paraneoplastic syndromes associated with anal squamous cell carcinoma (scc) are rare. Erythema gyratum repens (egr) is a cutaneous paraneoplastic syndrome with distinctive characteristics. Here, we report the rare case of a 73-year-old woman with a chronic erythematous rash for 11 months associated with intense pruritus. She was treated with prednisone and antihistamines by dermatologists, but did not respond. The patient was subsequently seen in our clinic for unintentional weight loss and anorexia with intermittent nausea and vomiting. During further evaluation with imaging studies, upper endoscopy, and colonoscopy with biopsy, poorly differentiated anal scc was identified. Biopsies of the skin rash were characteristic of egr. She was treated using concurrent chemotherapy with 5-fluorouracil and mitomycin C and pelvic radiation (50.4 Gy in 28 fractions) for anal scc. She tolerated the treatment, and her rash faded, with resolution of the pruritus.

The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A.

BACKGROUND: A recently published Position Statement (PS) by the Preimplantation Genetics Diagnosis International Society (PGDIS) regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF) contained inaccuracies and misrepresentations. Because opinions issued by the PGDIS have since 2016 determined worldwide IVF practice, corrections appear of importance. METHODS: The International Do No Harm Group in IVF (IDNHG-IVF) is a spontaneously coalesced body of international investigators, concerned with increasing utilization of add-ons to IVF. It is responsible for the presented consensus statement, which as a final document was reached after review of the pertinent literature and again revised after the recent publication of the STAR trial and related commentaries. RESULTS: In contrast to the PGDIA-PS, we recommend restrictions to the increasing, and by IVF centers now often even mandated, utilization of PGT-A in IVF cycles. While PGT-A has been proposed as a tool for achieving enhanced singleton livebirth outcomes through embryo selection, continued false-positive rates and increasing evidence for embryonic self-correction downstream from the testing stage, has led IDNHG-IVF to conclude that currently available data are insufficient to impose overreaching recommendations for PGT-A utilization. DISCUSSION: Here presented consensus offers an alternative to the 2019 PGDIS position statement regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF). Mindful of what appears to offer best outcomes for patients, and in full consideration of patient autonomy, here presented opinion is based on best available evidence, with the goal of improving safety and efficacy of IVF and minimizing wastage of embryos with potential for healthy births. CONCLUSIONS: As the PGDIS never suggested restrictions on clinical utilization of PGT-A in IVF, here presented rebuttal represents an act of self-regulation by parts of the IVF community in attempts to control increasing utilization of different unproven recent add-ons to IVF.

Latent genital tuberculosis adversely affects the ovarian reserve in infertile women.

STUDY QUESTION: What is the effect of latent genital tuberculosis (GTB) on ovarian reserve in infertile women? SUMMARY ANSWER: Women with latent GTB have lower ovarian reserves and yield lower numbers of oocytes in IVF. WHAT IS KNOWN ALREADY: Limited evidence suggests that women with GTB may have a low ovarian reserve. Infertile women have a high incidence of latent GTB and treatment improves fertility outcomes. STUDY DESIGN, SIZE, DURATION: This prospective study from February 2013 to January 2016 compared 431 infertile women diagnosed with latent GTB (Group I) to 453 infertile women without latent GTB (Group II). PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at Shreyas Hospital, Kolhapur, India, a tertiary referral centre for infertility. Women of both groups were 21-38 years of age. Group I consisted of infertile women with proven tubal patency but with latent GTB diagnosed by DNA PCR testing of an endometrial biopsy. Day 2-4 anti-Mullerian hormone (AMH) and antral follicle count (AFC) were assessed in both groups. All women with latent GTB took antituberculosis therapy (ATT). Gonadotropin dosages and oocyte and embryo details were noted in both groups for those who underwent IVF. MAIN RESULTS AND THE ROLE OF CHANCE: Women with latent GTB were younger (29.8 ± 4.4 years vs. 30.8 ± 4.5 years; P = 0.003) and, following adjustment for age, had significantly lower AMH [Median (IQR): 2 (0.9, 4.1) ng/ml vs 2.8 (1.3, 5) ng/ml; P = 0.01] and AFC [Median (IQR): 7 (5, 11) vs 8 (5, 14); P < 0.001]. Post ATT, women with latent GTB yielded fewer oocytes (9.3 ± 7.6 vs. 10.9 ± 8.1; P = 0.01), but had more grade I embryos transferred (1.1 ± 0.5 vs. 0.89 ± 1.0; P = 0.001) and a better implantation rate (26.8% vs. 17.5%; P = 0.004) in IVF compared to women in Group II. Group I had a higher pregnancy rate compared to Group II (51.6% vs. 40.5%; P = 0.001), through various treatment modalities. Considering the adequacy of the sample size and use of robust ovarian reserve markers, the role of chance is minimal. LIMITATIONS REASONS FOR CAUTION: The study is limited to an infertile population visiting a tertiary referral centre. The mechanisms by which latent GTB infection would lead to ovarian damage are unclear. WIDER IMPLICATIONS OF THE FINDINGS: It is believed that latent GTB is without any clinical significance. However, a low ovarian reserve in young women with latent GTB necessitates considering it as a cause of infertility, in women with prolonged infertility. These women may experience an accelerated decline in ovarian reserve with reduced success in achieving biological parenthood. Clinicians must be aware of this condition and its consequences while managing infertility. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Sushrut Assisted Conception Clinic, Shreyas Hospital, Kolhapur, India. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Age does not adversely influence outcomes among patients older than 60 years who undergo allogeneic hematopoietic stem cell transplant for AML and myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplant (AHSCT) outcomes data of older AML/myelodysplastic syndrome (MDS) patients are limited. We retrospectively evaluated consecutive patients ⩾60 years old with AML/MDS who underwent AHSCT between January 2005 and December 2014. The primary objectives were to determine nonrelapse mortality (NRM), relapse, relapse-free survival (RFS) and overall survival (OS) at 1 year post AHSCT. A total of 159 patients underwent AHSCT with a median age of 64 (range, 60-75) years. Of these, 103 patients (65%) had AML and 56 patients (35%) had MDS. At 1 year post AHSCT, grade III-IV acute GvHD and chronic GvHD occurred in 20.8% (95% confidence interval (CI), 14.9-27.5%) and 54.1% (95% CI, 46.0-61.5%) of patients, respectively. NRM, RFS, relapse rate and OS at 1 year post AHSCT were 25.3% (95% CI, 18.8-32.3%), 53.3% (95% CI, 46.1-61.7%), 21.4% (95% CI, 15.4-28.1%) and 56.4% (95% CI, 49.2-54.7%), respectively. High disease risk index was associated with poor RFS, OS and higher relapse rate (P<0.03), whereas non-thymoglobulin-based GvHD prophylaxis, higher comorbidity index (⩾3) and MDS were associated with higher NRM (P<0.03). Importantly, age did not have an adverse effect on NRM, relapse, RFS and OS. AHSCT was well tolerated. Hence, older age alone should not be considered a contraindication to AHSCT.

Identification of motility-associated progesterone-responsive differentially phosphorylated proteins.

Progesterone is one of the regulators of sperm motility and hyperactivation. In human spermatozoa, the effects of progesterone are thought to be mediated by protein phosphorylation. In the present study, we identified 22 proteins that are differentially phosphorylated (12 phosphorylated and 10 dephosphorylated) by progesterone in human spermatozoa. Functionally, the differentially phosphorylated proteins are predicted to have cytoskeletal localisation and to be associated with sperm motility. 5µM of progesterone to capacitated increased the phosphorylation of tyrosine residues in the principal piece and protein tyrosine kinase activity increased by almost 3.5-fold. For the first time, we demonstrate that tyrosine phosphatases are also activated in response to progesterone and that inhibition of tyrosine phosphatases attenuates dephosphorylation of flagellar proteins. We propose that progesterone activates both kinase and phosphatase pathways, leading to changes in the phosphorylation of many proteins in sperm flagella to increase motility.

PAX2 function, regulation and targeting in fallopian tube-derived high-grade serous ovarian cancer.

The fallopian tube epithelium (FTE) is one of the progenitor populations for high-grade serous ovarian cancer (HGSC). Loss of PAX2 is the earliest known molecular aberration in the FTE occurring in serous carcinogenesis followed by a mutation in p53. Pathological studies report consistent loss of PAX2 in benign lesions as well as serous tumors. In the current study, the combined loss of PAX2 and expression of the R273H p53 mutant protein in murine oviductal epithelial (MOE) cells enhanced proliferation and growth in soft agar in vitro but was insufficient to drive tumorigenesis in vivo. A serially passaged model was generated to investigate the role of aging, but was also insufficient to drive tumorigenesis. These models recapitulate early benign lesions and suggest that a latency period exists between loss of PAX2, p53 mutation and tumor formation. Stathmin and fut8 were identified as downstream targets regulated by loss of PAX2 and mutation of p53 in MOE cells. Re-expression of PAX2 in PAX2-null human HGSC cells reduced cell survival via apoptosis. Phosphatase and tensin homolog (PTEN)shRNA negatively regulated PAX2 expression and stable re-expression of PAX2 in MOE:PTENshRNA cells significantly reduced proliferation and peritoneal tumor formation in athymic nude mice. PAX2 was determined to be a direct transcriptional target that was activated by wild-type p53, whereas mutant p53 inhibited PAX2 transcription in MOE cells. A small molecule screen using the proximal PAX2 promoter driving luciferase identified four small molecules that were able to enhance PAX2 mRNA expression in MOE cells. PAX2 re-expression in HGSC cells and PTEN-deficient oviductal tumors may have the potential to induce apoptosis. In summary, mutant p53 and PTEN loss negatively regulated PAX2 and PAX2 re-expression in HGSC cells induced cell death.

Polymorphisms of IL-17 and ICAM-1 and their expression in Guillain-Barré syndrome.

PURPOSE: Guillain-Barré syndrome (GBS) is an acute inflammatory, autoimmune disorder of peripheral nervous system. Interleukin-17 (IL-17) and intercellular adhesion molecule-1 (ICAM-1) polymorphisms with higher expression levels have already been studied in many inflammatory and autoimmune diseases. However, the possible role of IL-17 and ICAM-1 polymorphisms in GBS remains unknown. Therefore, the current study investigated IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms. MATERIALS AND METHOD: In this study, total 80 GBS patients and 75 normal healthy controls were included. IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms were performed using polymerase chain reaction -restriction fragment length polymorphism analysis. Further, the expression of ICAM-1 and IL-17 was determined by reverse-transcriptase PCR and enzyme-linked immunosorbent assay. RESULTS: IL-17 (Glu126Gly) mutant and ICAM-1 (Gly241Arg) heterozygous genotypes were strongly associated with increased risk of GBS (p < 0.016; OR = 3.706, 95% CI = 1.28-10.67; p < 0.001; OR = 4.148, 95% CI = 2.119-8.119, respectively). IL-17 and ICAM-1 genes showed significantly higher expression in GBS when compared with healthy controls. CONCLUSION: IL-17 and ICAM-1 polymorphisms showed significant association with GBS and their enhanced expressions have possible role in GBS development. IL-17 and ICAM-1 polymorphisms could be genetic markers to GBS susceptibility.

Accessing completeness of pregnancy, delivery, and death registration by Accredited Social Health Activists [ASHA] in an innovative mHealth project in the tribal areas of Gujarat: A cross-sectional study.

BACKGROUND: The Innovative Mobile-phone Technology for Community Health Operation (ImTeCHO) is a mobile-phone application that helps Accredited Social Health Activists (ASHAs) in complete registration through the strategies employed during implementation that is linking ASHAs' incentives to digital records, regular feedback, onsite data entry, and demand generation among beneficiaries. OBJECTIVE: To determine the proportion of pregnancies, deliveries, and infant deaths (events) being registered through the ImTeCHO application against actual number of events in a random sample of villages. MATERIALS AND METHODS: Five representative villages were randomly selected from the ImTeCHO project area in the tribal areas of Gujarat, India to obtain the required sample of 98 recently delivered women. A household survey was done in the entire villages to enumerate each family and create a line-listing of events since January 2014; the line-listing was compared with list of women registered through the ImTeCHO application. The proportion of events being registered through the ImTeCHO application was compared against the actual number of events to find sensitivity of the ImTeCHO application. RESULT: A total of 844 families were found during household enumeration. Out of actual line-listing of pregnancies (N = 39), deliveries (N = 102), and infant deaths (N = 5) found during household enumeration, 38 (97.43%), 101 (99.01%), and 5 (100%) were registered by ASHAs through the ImTeCHO application. CONCLUSION: The use of mobile-phone technology and strategies applied during the ImTeCHO implementation should be upscaled to supplement efforts to improve the completeness of registration.

Association of NOD1 and NOD2 polymorphisms with Guillain-Barré syndrome in Northern Indian population.

BACKGROUND: Nucleotide oligomerization domain (NOD) proteins are cytosolic pattern recognition receptors that respond to bacterial substrate and induce NF-κB activation in host. Association of NOD polymorphisms have been studied in many autoimmune disorders, however its role in Guillain-Barré syndrome (GBS) remains unknown. We have investigated NOD1 Glu266Lys and NOD2 (Arg702Trp and Gly908Arg) gene polymorphisms among patients with GBS. MATERIALS AND METHOD: Polymorphisms in NOD-1 (Glu266Lys) and NOD-2 (Arg702Trp and Gly908Arg) genes were studied using polymerase chain reaction-restriction fragment length polymorphism in 105 patients with GBS and 100 healthy controls. RESULTS: Homozygous genotype (Lys/Lys) of NOD1 was significantly associated with GBS (p=0.013); and its subtypes viz. acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) (p=0.008 and p=0.024 respectively) than controls. In NOD2 (Arg702Trp and Gly908Arg) polymorphisms, only heterozygous genotype (Arg/Trp and Gly/Arg) showed significant association with GBS (p=0.001 and p=0.01 respectively); subtypes AMAN, acute motor-sensory axonal neuropathy (AMSAN) and AIDP showed association with heterozygote Arg702Trp (p=0.001; p=0.029 and p=0.001 respectively) whereas only AIDP was associated with heterozygote genotype Gly908Arg (p=0.003). CONCLUSION: NOD1 (Glu266Lys) and NOD2 (Arg702Trp and Gly908Arg) polymorphisms were associated with an increased susceptibility to GBS. These polymorphisms could be genetic marker to GBS susceptibility.

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions.

PURPOSE: The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility METHODS: Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated. RESULTS: Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group. CONCLUSION: AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.

Regulatory and effector T cells changes in remission and resistant state of childhood nephrotic syndrome.

Idiopathic minimal change disease is a disorder of T-cell dysfunction. The relative predominance of regulatory T cells (Tregs), Th1, and Th2 cells in nephrotic syndrome (NS) remains controversial. Imbalance in peripheral blood regulatory and effector T cells (Teff) are linked to cell mediated immune response and may be associated with steroid response in NS. Peripheral blood CD4 + CD25 + FoxP3 + (Tregs), CD4 + IFN-γ(+) (Th1), and CD4 + IL-4 + (Th2) lymphocytes were analyzed in 22 steroid-sensitive NS (SSNS) patients in sustained remission, 21 steroid-resistant NS (SRNS) and 14 healthy controls. The absolute percentage values and ratio of Th1/Tregs, Th2/Tregs, and Th1/Th2 were compared between SSNS, SRNS and control subjects. The percentage of Tregs was lower in SRNS patients (P = 0.001) compared with that of SSNS and healthy control. The percentage of Th1 cells was higher in SRNS (P = 0.001) compared to that of SSNS patients; however, it was similar to healthy controls (P = 1.00). The percentage of Th2 cells in SRNS (P = 0.001) was higher as compared to SSNS and controls. The ratio of Th1/Treg cells in SRNS (P = 0.001) was higher as compared to SSNS patients and controls. The ratio of Th2/Treg was also higher in SRNS as compared to SSNS and controls. The ratio of Th1/Th2 cells in SSNS, SRNS, and healthy controls were similar. The cytokines secretion complemented the change in different T-cell subtypes in SSNS, SRNS and healthy controls. However, the IFN-γ secretion in healthy controles was low inspite of similar percentage of Th1 cells among SRNS cases. We conclude that greater ratio of Tregs compared to that Th1 and Th2 favor steroid sensitivity and reverse ratio results in to SRNS. The difference in ratio is related to pathogenesis or it can be used as marker to predict steroid responsiveness needs further evaluation.

Y chromosome microdeletions in infertile men: prevalence, phenotypes and screening markers for the Indian population.

PURPOSE: Yq microdeletions are the leading genetic cause of male infertility and its detection is clinically relevant for appropriate genetic counseling. We aimed to determine the prevalence and type of Yq microdeletions, the associated seminal phenotypes and the STS markers that are relevant for its testing in Indian population. METHODS: Yq microdeletion analysis was carried out in 1,636 infertile cases in our centers. Additional data was collected from published studies in Indian population leading to a total of 3,647 cases. RESULTS: In our cohort, 3.4 % (56/1,636) of infertile men had Yq microdeletions. Combining the data from other published studies identified 215/3,647 (5.8 %) infertile individuals to harbor Yq microdeletions; with 6.4 % in azoopsermia, 5.8 % in oligozoospermia and 3.2 % in oligoasthenozoospermia and teratozoospermia cases. No significant differences in the deletion frequencies were observed between idiopathic vs non idiopathic cases (5.8 vs 8.6 % respectively). Deletions of AZFc were at highest frequency (46.6 %) with double deletions most commonly observed in azoospermic subjects. With respect to the STS markers, screening with the six European Academy of Andrology (EAA) markers would miss 3.1 % of cases; additional non EAA markers that would contribute significantly to screening are sY746, sY82, sY121, sY128, sY130, sY143, sY145 & sY160. INTERPRETATIONS AND CONCLUSIONS: The frequency of Yq microdeletions is lower in Indian population as compared to Western counterparts. There is no major association of Yq microdeletions with seminal parameters or cause of infertility. Clinically it will be necessary to offer Yq microdeletion testing to all the classes of infertile men. The EAA markers may not be adequate to detect microdeletions in Indian infertile men.

Progesterone activates Janus Kinase 1/2 and activators of transcription 1 (JAK1-2/STAT1) pathway in human spermatozoa.

Ejaculated spermatozoa undergo capacitation and acrosome reaction by responding to extrinsic clues and activate signalling cascades to induce protein tyrosine phosphorylation. In the present study, we investigated the existence, the Janus kinase (JAK) and activator of transcription (STAT) pathway and determined its physiological relevance. JAK1 and STAT1 are localised on the equatorial region and the midpiece of their human spermatozoa, JAK2 is detected on the sperm tail. Capacitation leads to phosphorylation of JAK2 but not JAK1 and STAT1. In the uncapacitated sperm, phosphorylated JAK2 (pJAK2) is localised mainly in the tail region; in response to capacitation, the JAK2 is phosphorylated in the midpiece and the head region along with the tail. Progesterone (5 µm) leads to phosphorylation of JAK1, JAK2 and STAT1 in a time-dependent manner. In progesterone-treated spermatozoa, the JAK2 in the tail is hyperphosphorylated, the JAK2 in the head and the midpiece is dephosphorylated. We conclude that in human spermatozoa, the JAK1/2 pathway is activated upon capacitation and is further modulated by progesterone; the biological processes controlled by this pathway in sperm need to be elucidated.

Differential concentration and time dependent effects of progesterone on kinase activity, hyperactivation and acrosome reaction in human spermatozoa.

Progesterone has been identified to be one of the physiological regulators of sperm hyperactivation and acrosome reaction. However, the high sensitivity of human spermatozoa to progesterone implies that many may undergo premature hyperactivation and acrosome reaction thereby compromising their ability to fertilize. We hypothesized that if a spermatozoon has to preclude the occurrence of these events prematurely, there should be differential dose- and time-dependent effects on motility and acrosome reaction. We observed that low concentrations of progesterone (10 and 100 nm) induce sperm motility and activate tyrosine kinase; higher concentrations (1-10 µm) are required to induce extracellular signal regulated kinases 1/2 (Erk1/2), p90 ribosomal S6 kinase (p90RSK), p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK1) and AKT phosphorylation, hyperactivation and acrosome reaction. The induction of acrosome reaction and tyrosine phosphorylation in response to higher concentration of progesterone is not absolutely dependent on activation of T-type voltage-gated Ca(2+) channel or CatSper as Mibefradil did not completely abrogate progesterone-mediated effects. These results imply that although the spermatozoa are sensitive to low concentrations of progesterone, they only activate motility and tyrosine kinase activation; higher concentrations are required to induce hyperactivation and acrosome reaction probably by activating multiple kinase pathways including the MAPK and AKT.

Treatment of ruptured ICA during transsphenoidal surgery. Two different endovascular strategies in two cases.

Rupture of the internal carotid artery (ICA) during transsphenoidal surgery is a rare but potentially lethal complication. Direct surgical repair of the ICA may be difficult and time-consuming in an acute setting. Urgent endovascular treatments with vascular plug or stent-graft have been the feasible options to date. We desrcibe two cases of iatrogenic rupture of ICA during transsphenoidal surgery. In the first case we occluded the ICA with a vascular plug at the site of tear where cross circulation was adequate. In the second case we had to preserve the ICA with stent-graft since there was no adequate cross circulation. These two strategies are discussed below.

Cutaneous annular sarcoidosis developing on a background of exogenous ochronosis: a report of two cases and review of the literature.

Exogenous (cosmetic) ochronosis is caused by the long term use of skin-lightening creams containing hydroquinone. Three cases of systemic sarcoidosis with cutaneous sarcoidal granulomas, which developed on ochronotic skin were last described by Jacyk in 1995. Dogliotti and Leibowitz previously reported cases of granulomatous ochronosis with sarcoid-like histological changes but with no associated systemic sarcoidosis. We report two additional cases of cutaneous sarcoidal granulomas, which developed on a background of cosmetic ochronosis in patients recently diagnosed with systemic sarcoidosis.